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Pubblicazioni recenti - cardiac hypertrophy
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Integrating Measures of Myocardial Fibrosis in the Transition from Hypertensive Heart Disease to Heart Failure.
Curr Hypertens Rep2021 Apr;23(4):22. doi: 10.1007/s11906-021-01135-8.
Stacey R Brandon, Hundley W Gregory,
Abstract
PURPOSE OF REVIEW:
This review aims to summarize recent developments in identifying and quantifying both the presence and amount of myocardial fibrosis by imaging and biomarkers. Further, this review seeks to describe in general ways how this information may be used to identify hypertension and the transition to heart failure with preserved ejection fraction.
RECENT FINDINGS:
Recent studies using cardiac magnetic resonance imaging highlight the progressive nature of fibrosis from normal individuals to those with hypertension to those with clinical heart failure. However, separating hypertensive patients from those with heart failure remains challenging. Recent studies involving echocardiography show the subclinical myocardial strain changes between hypertensive heart disease and heart failure. Lastly, recent studies highlight the potential use of biomarkers to identify those with hypertension at the greatest risk of developing heart failure. In light of the heterogeneous nature between hypertension and heart failure with preserved ejection fraction, an integrated approach with cardiac imaging and biomarker analysis may enable clinicians and investigators to more accurately characterize, prevent, and treat heart failure in those with hypertension.
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Cardioprotective effects of transplanted adipose-derived stem cells under Ang II stress with Danggui administration augments cardiac function through upregulation of insulin-like growth factor 1 receptor in late-stage hypertension rats.
Environ Toxicol2021 Apr;():. doi: 10.1002/tox.23145.
Barik Parthasarathi, Shibu Marthandam Asokan, Hsieh Dennis Jine-Yuan, Day Cecilia Hsuan, Chen Ray-Jade, Kuo Wei-Wen, Chang Yung-Ming, Padma V Vijaya, Ho Tsung-Jung, Huang Chih-Yang,
Abstract
In aging hypertensive conditions, deterioration of insulin-like growth factor 1 receptor (IGF1R) cause a pathological impact on hypertensive hearts with an increased Ang II level. Recovering these adverse conditions through transplanted adipose-derived stem cells is a challenging approach. Moreover, Danggui, a Traditional Chinese medicine (TCM), is used for the treatment of cardioprotective effects. In this study, to evaluate whether the combined effect of MSCs and TCM can recover the cardiac function in late-stage hypertension rats. We observed that lower dose of Danggui crude extract treatment showed an increased level of cell viability with maintained stemness properties and growth rate in rat adipose-derived stem cells (rADSCs). Further, we cocultured the H9c2 cells with rADSCs and the results revealed that Danggui-treated MSCs enhanced the IGF1R expression and attenuated the hypertrophy in H9c2 cells against Ang II challenge by immunoblot and rhodamine-phalloidin staining. In addition, Danggui crude extract was also quantified and characterized by HPLC and LC-MS analysis. Furthermore, the in vivo study was performed by considering 11?months old rats (n = 7). Importantly, the oral administration of Danggui crude extract with stem cells intravenous injection in SHR-D-ADSCs group showed a combination effect to augment the cardiac function through enhancement of ejection fraction, fractional shortening, contractility function in the late-stage hypertension conditions. We have also observed a decreased apoptosis rate in the heart tissue of SHR-D-ADSCs group. Taken together, these results indicate that the combinatorial effects of Danggui crude extract and stem cell therapy enhanced cardiac function in late-stage SHR rats.
© 2021 Wiley Periodicals LLC.
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Epidemiology of Heart Failure Stages in Middle-Aged Black People in the Community: Prevalence and Prognosis in the Atherosclerosis Risk in Communities Study.
J Am Heart Assoc2021 Apr;():e016524. doi: 10.1161/JAHA.120.016524.
Vasan Ramachandran S, Musani Solomon K, Matsushita Kunihiro, Beard Walter, Obafemi Olushola B, Butler Kenneth R, Chang Patricia P, Mosley Thomas H, Fox Ervin,
Abstract
Background Black individuals have a higher burden of risk factors for heart failure (HF) and subclinical left ventricular remodeling. Methods and Results We evaluated 1871 Black participants in the Atherosclerosis Risk in Communities Study cohort who attended a routine examination (1993-1996, median age 58 years) when they underwent echocardiography. We estimated the prevalences of 4 HF stages: (1) : no risk factors; (2) : presence of HF risk factors (hypertension, diabetes mellitus, obesity, smoking, dyslipidemia, coronary artery disease without clinical myocardial infarction), no cardiac structural/functional abnormality; (3) : presence of prior myocardial infarction, systolic dysfunction, left ventricular hypertrophy, regional wall motion abnormality, or left ventricular enlargement; and (4) : prevalent HF. We assessed the incidence of clinical HF, atherosclerotic cardiovascular disease events, and all-cause mortality on follow-up according to HF stage. The prevalence of HF Stages 0, A, B, and C/D were 3.8%, 20.6%, 67.0%, and 8.6%, respectively, at baseline. On follow-up (median 19.0 years), 309 participants developed overt HF, 390 incurred new-onset cardiovascular disease events, and 651 individuals died. Incidence rates per 1000 person-years for overt HF, cardiovascular disease events, and death, respectively, were Stage 0, 2.4, 0.8, and 7.6; Stage A, 7.4, 9.7, and 13.5; Stage B 13.6, 15.9, and 22.0. Stage B HF was associated with a 1.5- to 2-fold increased adjusted risk of HF, cardiovascular disease events and death compared with Stages 0/A. Conclusions In our large community-based sample of Black individuals, we observed a strikingly high prevalence of Stage B HF in middle age that was a marker of high cardiovascular morbidity and mortality.
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Effect of Isolated Obesity on Left Ventricular Function and Structure: A Single-Center Experience.
Cureus2021 Mar;13(3):e13988. doi: 10.7759/cureus.13988.
AlRahimi Jamilah, Aboud Abdulbari, AlQuhaibi Abdullah S, Almaghrabi Yazan, Alghamdi Yousef S, Mufti Hani N,
Abstract
Background and objectives Obesity can increase cardiac mass and affect cardiac performance independently from other risk factors. Several studies have identified an association in patients who already have comorbidities, however, few studies focused on obesity as an isolated risk factor. This study aimed to assess the associations between isolated obesity and heart morphological and functional characteristics. Methods This was a cross-sectional study that recruited 114 patients referred for echocardiographic study in King Faisal Cardiac Center. Adult patients who had a body mass index (BMI) above 25 kg/m were included, while patients with comorbidities such as hypertension, diabetes mellitus, dyslipidemia, or those who use medications for chronic diseases were excluded from this study. Variables of interest that we collected were age, gender, weight, BMI, and those related to morphological and functional changes in the heart including left ventricular mass index (LVMI), LV end-diastolic volume, and left ventricular ejection fraction (LVEF). Results Most of the study participants (63.8%) were class II or class III obesity and about 80% were males. The mean ± SD of LVEF was 55.7% ± 2.8%, while the mean of the left ventricular mass index was 28.5±5.84. The mean of LV end-diastolic volume index (LVEDVI) was slightly higher among males than females (48.8±11.6 versus 46.4±11.7 ml/m), however, this difference was not statistically significant (p-value= 0.395). There was no correlation between BMI and LVMI in females (R - 0.226, R 0.05, P-value 0.37), while the LVMI was found to have a negative correlation between BMI and male gender that was significant (R - 0.292, R 0.09, P-value 0.0052). It was found that there is no correlation between LVEF and BMI for males and females (male= R 0.093, R0.032, P-value 0.093; female= R 0.172, R 0.029, P-value 0.434). With regards to the LVEDVI, there was a negative correlation between higher BMI and male gender that was significant (male= R - 0.396, R 0.157, P-value 0.0001) while it was not significant in females (R -0.0298, R 0.0009, P-value 0.893). Conclusions We have found that cardiac function is not affected by isolated obesity. However, indexed cardiac parameters like LVM and LV end diastolic volume were negatively correlated with higher BMI and positively correlated with relative wall thickness (RWT) only in males. This negative correlation might be one of the triggers to the development of obesity-induced cardiomyopathy.
Copyright © 2021, AlRahimi et al.
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Neonatal Myocardial Infarction in Association with Gestational Diabetes.
Can J Cardiol2021 Apr;():. doi: S0828-282X(21)00211-7.
Aly Safwat, Aguet Julien, Dragulescu Andrea, Grosse-Wortmann Lars,
Abstract
Fetal and neonatal hypertrophic cardiomyopathy is a complication of gestational diabetes and usually follows a benign course. In this report, we present a rare case of a newborn of a diabetic mother with severe ventricular hypertrophy who developed myocardial infarction (MI) confirmed by elevated cardiac enzymes, electrocardiographic changes as well as subendocardial ischemia on CMR imaging. Follow up revealed complete functional myocardial recovery with normalization of ventricular systolic and diastolic functions on serial echocardiograms.
Copyright © 2021. Published by Elsevier Inc.
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Fibroblast GATA-4 and GATA-6 promote myocardial adaptation to pressure overload by enhancing cardiac angiogenesis.
Basic Res Cardiol2021 Apr;116(1):26. doi: 10.1007/s00395-021-00862-y.
Dittrich Gesine M, Froese Natali, Wang Xue, Kroeger Hannah, Wang Honghui, Szaroszyk Malgorzata, Malek-Mohammadi Mona, Cordero Julio, Keles Merve, Korf-Klingebiel Mortimer, Wollert Kai C, Geffers Robert, Mayr Manuel, Conway Simon J, Dobreva Gergana, Bauersachs Johann, Heineke Joerg,
Abstract
Heart failure due to high blood pressure or ischemic injury remains a major problem for millions of patients worldwide. Despite enormous advances in deciphering the molecular mechanisms underlying heart failure progression, the cell-type specific adaptations and especially intercellular signaling remain poorly understood. Cardiac fibroblasts express high levels of cardiogenic transcription factors such as GATA-4 and GATA-6, but their role in fibroblasts during stress is not known. Here, we show that fibroblast GATA-4 and GATA-6 promote adaptive remodeling in pressure overload induced cardiac hypertrophy. Using a mouse model with specific single or double deletion of Gata4 and Gata6 in stress activated fibroblasts, we found a reduced myocardial capillarization in mice with Gata4/6 double deletion following pressure overload, while single deletion of Gata4 or Gata6 had no effect. Importantly, we confirmed the reduced angiogenic response using an in vitro co-culture system with Gata4/6 deleted cardiac fibroblasts and endothelial cells. A comprehensive RNA-sequencing analysis revealed an upregulation of anti-angiogenic genes upon Gata4/6 deletion in fibroblasts, and siRNA mediated downregulation of these genes restored endothelial cell growth. In conclusion, we identified a novel role for the cardiogenic transcription factors GATA-4 and GATA-6 in heart fibroblasts, where both proteins act in concert to promote myocardial capillarization and heart function by directing intercellular crosstalk.
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Left-ventricular hypertrophy in 18-month-old donor rat hearts was not associated with graft dysfunction in the early phase of reperfusion after cardiac transplantation-gene expression profiling.
Geroscience2021 Apr;():. doi: 10.1007/s11357-021-00348-8.
Korkmaz-Icöz Sevil, Akca Deniz, Li Shiliang, Loganathan Sivakkanan, Brlecic Paige, Ruppert Mihály, Sayour Alex Ali, Simm Andreas, Brune Maik, Radovits Tamás, Karck Matthias, Szabó Gábor,
Abstract
The use of hearts with left-ventricular (LV) hypertrophy (LVH) could offer an opportunity to extend the donor pool for cardiac transplantation. We assessed the effects of LVH in 18-month-old spontaneously hypertensive stroke-prone (SHRSP) donor rats and following transplantation. In donors, cardiac function and structural alterations were assessed. Then, the hearts were transplanted into young normotensive-rats. We evaluated LV graft function 1 h after transplantation. The myocardial expression of 92 genes involved in apoptosis, inflammation, and oxidative-stress was profiled using PCR-array. Compared to controls, SHRSP-rats developed LVH, had increased LV systolic performance (slope of the end-diastolic pressure-volume (PV) relationship: 1.6±0.2 vs 0.8±0.1mmHg/?l, p<0.05) accompanied by diastolic dysfunction [prolonged time constant of LV pressure decay (Tau: 15.8±0.6 vs 12.3±0.5ms) and augmented diastolic stiffness (LV end-diastolic PV relationship: 0.103±0.012 vs 0.045±0.006mmHg/ml), p<0.05]. They presented ECG changes, myocardial fibrosis, and increased nitrotyrosine immunoreactivity and plasma troponin-T and creatine kinase-CM levels. After transplantation, even though the graft contractility was better in SHRSP rats compared to controls, the adverse impact of ischemia/reperfusion-injury on contractility was not altered (E ratio after versus before transplantation: 32% vs 29%, p>0.05). Whereas nitrotyrosine immunoreactivity was higher, myeloperoxidase-positive cell infiltration was decreased in the SHRSP+transplanted compared to control+transplanted. Among the tested genes, LVH was associated with altered expression of 38 genes in donors, while transplantation of these hearts resulted in the change of four genes. Alterations in 18-month-old donor hearts, as a consequence of hypertension and LVH, were not associated with graft dysfunction in the early phase of reperfusion after transplantation.
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Effects of physical exercise combined with captopril or losartan on left ventricular hypertrophy of hypertensive rats.
Clin Exp Hypertens2021 Apr;():1-14. doi: 10.1080/10641963.2021.1907399.
Tomaz de Castro Quênia Janaína, Araujo Carolina Morais, Watai Patrícia Yoshie, Silva Samara Stéfani de Castro, de Lima Wanderson Geraldo, Becker Lenice Kappes, Locatelli Jamille, Guimarães Homero Nogueira, Grabe-Guimarães Andrea,
Abstract
Left ventricular hypertrophy (LVH) is an endpoint of hypertensive cardiac alterations. Renin-angiotensin-aldosterone system (RAAS) blockers are among the most effective on LVH regression. Physical exercise combined to antihypertensive drug contributes to arterial pressure (AP) control and LVH prevention. We evaluated the effects of physical exercise combined to captopril or losartan during eight weeks for spontaneously hypertensive rats (SHR) on some cardiac parameters. SHR (n=5-6 per group) were sedentary or trained 5 days a week in treadmill during 8 weeks; and they were treated with daily oral captopril (12.5, 25, or 50mg/kg), losartan (2.5, 5, or 10mg/kg), or vehicle. At the end, it was obtained systolic AP (SAP), electrocardiogram (ECG), and hearts metalloproteinase 2 (MMP-2) activity and histology. Captopril 25 and 50 mg/kg, and losartan 10 mg/kg lowered SAP of sedentary and trained SHR. Losartan 5 mg/kg combined with physical exercise also lowered SAP. Combined with exercise, captopril 50 mg/kg lowered 13.6% of QT interval, 14.2% of QTc interval, and 22.8% of Tpeak-Tend compared to sedentary SHR. Losartan 5 and 10mg/kg lowered QT interval of sedentary and trained SHR. Losartan 2.5, 5 and 10mg/kg combined with physical exercise lowered respectively 25.4%, 24.8%, and 31.8% of MMP-2 activity. Losartan (10mg/kg) combined with exercise reduced cardiomyocyte diameter. These data support the hypothesis of physical exercise combined with RAAS blockers could improve the benefits on hypertensive LVH treatment.
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Krüppel-Like Factor 15 Modulates Signaling-Mediated Inflammatory Response Contributing to Angiotensin II-Induced Cardiac Remodeling.
Front Cell Dev Biol2021 ;9():644954. doi: 10.3389/fcell.2021.644954.
He Shun, Lu Yuanyuan, Guo Yuetong, Li Shijin, Lu Xiao, Shao Shuai, Zhou Handan, Wang Ruiqi, Wang Jiguang, Gao Pingjin, Li Xiaodong,
Abstract
Inflammation is involved in cardiac remodeling. In response to pathological stimuli, activated cardiac fibroblasts (CFs) secreting inflammatory cytokines and chemokines play an important role in monocyte/macrophage recruitment. However, the precise mechanism of CF-mediated inflammatory response in hypertension-induced cardiac remodeling remains unclear. In the present study, we investigated the role of transcription factor Krüppel-like factor 15 (KLF15) in this process. We found that KLF15 expression decreased while chemokine and its receptor expression increased in the hearts of angiotensin II (Ang II)-infused mice. Compared to the wild-type mice, KLF15 knockout (KO) mice aggravated Ang II-induced cardiac hypertrophy and fibrosis. Deficiency of KLF15 promoted macrophage accumulation, increase of and expression, and mTOR, ERK1/2, NF-?B-p65 signaling activation in the hearts. Mechanistically, Ang II dose- dependently decreased KLF15 expression and increased secretion from cardiac fibroblasts but not cardiac myoblasts. Loss- or gain-of-function studies have shown that KLF15 negatively regulated expression through its transactivation domain (TAD). Intriguingly, the adenovirus-mediated full length of KLF15-but not KLF15 with TAD deletion overexpression-markedly prevented pathological change in Ang II-infused mice. Notably, the administration of inhibitor SB265610 reversed KLF15 knockout-mediated aggravation of cardiac dysfunction, remodeling, and inflammation induced by Ang II. In conclusion, our study identifies that KLF15 in cardiac fibroblasts negatively regulates axis-mediated inflammatory response and subsequent cardiac remodeling in hypertension.
Copyright © 2021 He, Lu, Guo, Li, Lu, Shao, Zhou, Wang, Wang, Gao and Li.
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Advances in Research on the Cardiovascular Complications of Acromegaly.
Front Oncol2021 ;11():640999. doi: 10.3389/fonc.2021.640999.
Yang Han, Tan Huiwen, Huang He, Li Jianwei,
Abstract
Cardiovascular-related complications are one of the most common complications in patients with acromegaly, and can lead to an increased risk of death. Hypertension and cardiomyopathy are the main cardiovascular complications. The characteristics of acromegalic cardiomyopathy are concentric biventricular hypertrophy and diastolic dysfunction. In addition, arrhythmia and heart valve disease are common cardiac complications in acromegaly. Although the underlying pathophysiology has not been fully elucidated, the spontaneous overproduction of GH and IGF-1, increasing age, prolonged duration of disease and the coexistence of other cardiovascular risk factors are crucial to cardiac complications in patients with acromegaly. Early diagnosis and appropriate treatment of acromegaly might be beneficial for the prevention of cardiomyopathy and premature death.
Copyright © 2021 Yang, Tan, Huang and Li.
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Subtle Role for Adenylate Kinase 1 in Maintaining Normal Basal Contractile Function and Metabolism in the Murine Heart.
Front Physiol2021 ;12():623969. doi: 10.3389/fphys.2021.623969.
Zervou Sevasti, McAndrew Debra J, Whittington Hannah J, Lake Hannah A, Park Kyung Chan, Cha Kuan Minn, Ostrowski Philip J, Eykyn Thomas R, Schneider Jürgen E, Neubauer Stefan, Lygate Craig A,
Abstract
Aims:
Adenylate kinase 1 (AK1) catalyses the reaction 2ADP ? ATP + AMP, extracting extra energy under metabolic stress and promoting energetic homeostasis. We hypothesised that increased AK1 activity would have negligible effects at rest, but protect against ischaemia/reperfusion (I/R) injury.
Methods and Results:
Cardiac-specific AK1 overexpressing mice (AK1-OE) had 31% higher AK1 activity ( = 0.009), with unchanged total creatine kinase and citrate synthase activities. Male AK1-OE exhibited mild dysfunction at baseline with lower LV pressure, impaired relaxation, and contractile reserve. LV weight was 19% higher in AK1-OE males due to higher tissue water content in the absence of hypertrophy or fibrosis. AK1-OE hearts had significantly raised creatine, unaltered total adenine nucleotides, and 20% higher AMP levels ( = 0.05), but AMP-activated protein kinase was not activated ( = 0.85). H-NMR revealed significant differences in LV metabolite levels compared to wild-type, with aspartate, tyrosine, sphingomyelin, cholesterol all elevated, whereas taurine and triglycerides were significantly lower. global no-flow I/R, caused four-of-seven AK1-OE hearts to develop terminal arrhythmia (cf. zero WT), yet surviving AK1-OE hearts had improved functional recovery. However, AK1-OE did not influence infarct size and arrhythmias were only observed , probably as an artefact of adenine nucleotide loss during cannulation.
Conclusion:
Modest elevation of AK1 may improve functional recovery following I/R, but has unexpected impact on LV weight, function and metabolite levels under basal resting conditions, suggesting a more nuanced role for AK1 underpinning myocardial energy homeostasis and not just as a response to stress.
Copyright © 2021 Zervou, McAndrew, Whittington, Lake, Park, Cha, Ostrowski, Eykyn, Schneider, Neubauer and Lygate.
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Pulmonary artery obstruction index, pulmonary artery diameter and right ventricle strain as prognostic CT findings in patient with acute pulmonary embolism.
Radiologia2021 Apr;():. doi: S0033-8338(21)00076-X.
Hajiahmadi S, Tabesh F, Shayganfar A, Shirani Fattane, Ebrahimian S,
Abstract
OBJECTIVE:
This study was designed to determine predictors of pulmonary hypertension and signs of right heart dysfunction caused by pulmonary embolism (PE) that may lead to early detection of high-risk patients. So the predictive value of pulmonary artery obstruction index (PAOI), measured by pulmonary CT angiography (PCTA) in the acute setting, in predicting the patients susceptible to PE cardiac complications was evaluated. Also two other PCTA indices, pulmonary artery diameter (PAD), and right ventricle (RV) strain, in these patients were investigated and their predictive value for cardiac complications on follow up echocardiography were demonstrated.
MATERIALS AND METHODS:
In the study 120 patients with a definite diagnosis of PE were included. The PAOI, PAD and RV strain were measured using PCTA at the time of the initial diagnosis. Transthoracic echocardiography was done 6 months after the diagnosis of PE and RV echocardiographic indices were measured. Pearson correlation was used to investigate correlation between PAOI, PAD, RV strain and signs of right heart dysfunction.
RESULTS:
PAOI was strongly correlated with systolic pulmonary artery pressure (SPAP) (r=0.83), RV systolic pressure (r=0.78) and RV wall thickness (r=0.61) in long-term follow up echocardiography. A higher rate of RV dysfunction and RV dilation was detected among the patients with higher PAOI (P<0.001). PAOI?18 was strongly predictive for development of RV dysfunction. Also developments of pulmonary hypertension, RV systolic hypertension, RV dilation, RV dysfunction, and RV hypertrophy were significantly more common among patients with higher PAD and RV strain (P<0.001).
CONCLUSIONS:
PAOI, PAD and RV strain are sensitive and specific PCTA indices that can predict the development of long-term complications such as pulmonary hypertension and right heart dysfunction, at the time of initial PE diagnosis.
Copyright © 2021 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.
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Cardiac thyrotropin-releasing hormone (TRH) inhibition improves ventricular function and reduces hypertrophy and fibrosis after myocardial infarction in rats.
J Card Fail2021 Apr;():. doi: S1071-9164(21)00124-X.
Schuman Mariano L, Diaz Ludmila S Peres, Aisicovich Maia, Ingallina Fernando, Toblli Jorge E, Landa Maria S, García Silvia I,
Abstract
BACKGROUND:
Cardiac thyrotropin-releasing hormone (TRH) is a tripeptide with still unknown functions. We demonstrated that the left ventricle (LV) TRH system is hyperactivated in spontaneously hypertensive rats and its inhibition prevented cardiac hypertrophy and fibrosis. Therefore, we evaluated whether in vivo cardiac TRH inhibition could improve myocardial function and attenuate ventricular remodeling in a rat model of myocardial infarction (MI).
METHODS AND RESULTS:
In Wistar rats, MI was induced by a permanent left anterior descending coronary artery ligation. A coronary injection of a specific siRNA against TRH was simultaneously applied. The control group received a scrambled siRNA. Cardiac remodeling variables were evaluated one week later. In MI rats, TRH inhibition decreased LV end-diastolic (1.049±0.102 vs. 1.339±0.102 ml, p<0.05), and end-systolic volumes (0.282±0.043 vs. 0.515±0.037 ml, p<0.001), and increased LV ejection fraction (71.89±2.80 vs. 65.69±2.85 %, p<0.05). Although both MI groups presented similar infarct size, siRNA-the TRH treatment attenuated the cardiac hypertrophy index and myocardial interstitial collagen deposition in the peri-infarct myocardium. These effects were accompanied by attenuation in the rise of TGF?, collagen I, and III and also the fetal genes (ANP, BNP, and ?MHC) expression in the peri-infarct region. Besides, the expression of Hif1? and VEGF significantly increased compared to all groups.
CONCLUSIONS:
Cardiac TRH inhibition improves LV systolic function and attenuates ventricular remodeling after MI. These novel findings support the idea that TRH inhibition may serve as a new therapeutic strategy against the progression of heart failure.
Copyright © 2021. Published by Elsevier Inc.
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High-mobility group box 1 serves as an inflammation driver of cardiovascular disease.
Biomed Pharmacother2021 Apr;139():111555. doi: S0753-3322(21)00340-1.
Wahid Abdul, Chen Wei, Wang Xuewen, Tang Xiaohong,
Abstract
Cardiovascular disease (CVD) is the most deadly disease, which can cause sudden death, in which inflammation is a key factor in its occurrence and development. High-mobility group box 1 (HMGB1) is a novel nuclear DNA-binding protein that activates innate immunity to induce inflammation in CVD. HMGB1 exists in the cytoplasm and nucleus of different cell types, including those in the heart. By binding to its receptors, HMGB1 triggers a variety of signaling cascades, leading to inflammation and CVD. To help develop HMGB1-targeted therapies, here we discuss HMGB1 and its biological functions, receptors, signaling pathways, and pathophysiology related to inflammation and CVD, including cardiac remodeling, cardiac hypertrophy, myocardial infarction, heart failure, pulmonary hypertension, atherosclerosis, and cardiomyopathy.
Copyright © 2021. Published by Elsevier Masson SAS.
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An Optimized Model of Hypertrophic Preconditioning Confers Cardioprotection in the Mouse.
J Surg Res2021 Apr;264():544-552. doi: S0022-4804(20)30870-2.
Cai Xiaojie, Tian Yuling, Wu Yue, Bonner Michael Y, Zhuo Xiaozhen, Yuan Zuyi,
Abstract
BACKGROUND:
Conventional models of hypertrophic preconditioning (C-HP) can be established surgically through transverse aortic constriction (TAC) ? deconstriction (De-TAC) ? reconstriction (Re-TAC) characterized by dynamic afterload while it exerts technical difficulty on operators and poses high mortality during perioperative period in mice. We aimed to introduce an optimized method for obtaining a hypertrophic preconditioning (O-HP) model for further study on cardiac hypertrophy.
METHODS:
Ninety mice were divided into four groups: sham, TAC, C-HP, and O-HP. The sham group was exerted on three-time thoracotomies. The TAC group experienced twice thoracotomies and one TAC operation. C-HP and O-HP groups were given TAC, De-TAC, and Re-TAC operation at day 0, day 3, and day 7 in conventional and optimized method, respectively. We optimized the operating procedure in O-HP mice compared with the C-HP group by (1) leaving a ?3-cm suture fixed in the subcutaneous layer after aortic constriction in TAC surgery (2) using two small forceps to untie the constriction knot instead of cutting it in the De-TAC operation. Ultrasound biomicroscopy was used for hemodynamics and cardiac function detection. Four weeks after the third surgery, all mice were sacrificed and pathology was analyzed among four groups.
RESULTS:
Four weeks after Re-TAC, the survival of O-HP mice was 63.3% while that of C-HP was 26.7%. Ultrasound biomicroscopy showed a successful establishment of HP models. C-HP and O-HP mice had improved cardiac structure and function indicated by left ventricular end-systolic diameter, left ventricular end-systolic posterior wall thickness, left ventricular ejection fraction, and left ventricular fractional shortening than the TAC group. Pathological analysis showed O-HP as well as C-HP had less hypertrophy than the TAC mice.
CONCLUSIONS:
Our results provide a rapid, safe, efficient, and reproducible method for optimized establishment of the HP model, which will facilitate studies for early intervention and prevention of left ventricular hypertrophy and heart failure.
Copyright © 2020 Elsevier Inc. All rights reserved.
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Determinants of cardiac structure in frail and sarcopenic elderly adults.
Exp Gerontol2021 Apr;150():111351. doi: S0531-5565(21)00126-1.
Pelà Giovanna, Tagliaferri Sara, Perrino Felice, Righelli Ilaria, Montanari Rossella, Longobucco Yari, Salvi Marco, Calvani Riccardo, Cesari Matteo, Cherubini Antonio, Bernabei Roberto, Di Bari Mauro, Landi Francesco, Marzetti Emanuele, Lauretani Fulvio, Maggio Marcello,
Abstract
BACKGROUND:
Cardiac structure and function change with age. The higher prevalence of left ventricular hypertrophy (LVH) with concentric remodeling is indicative of a typical geometric pattern of aging associated with a higher cardiovascular (CV) risk and diseases. The recent associations found between low left ventricular and skeletal mass in older patients with frailty and sarcopenia have raised great interest in investigating cardiac characteristics and determinants of left ventricular mass (LVM) in this population.
DESIGN:
Cross-sectional study.
METHODS:
We evaluated 100 sarcopenic and physically frail outpatients, 33 men (M), 67 women (F), aged ?70 years (mean age 79 ± 5) and enrolled in the Parma site of European multicenter SPRINTT population.
RESULTS:
All male and female participants showed LVH, assessed as indexed LVM to body surface area (LVM/BSA) (M = 128 ± 39 g/m; F = 104 ± 26 g/m), and were more prone to have concentric geometry, as demonstrated by relative wall thickness value (0.41 in both sexes). After backward regression analysis, including covariates such as age, sex, office or ABPM systolic blood pressure (SBP), heart rate, BSA, use of ? blockers, ACE-inhibitors, angiotensin receptor blockers, calcium channel blockers, diuretics, physical activity, hemoglobin level, and Mini Mental State examination - the most powerful determinants of LVM were clinical SBP (? = 1.51 ± 0.31, p = 0.0005), BSA (? = 165.9 ± 41.4, p = 0.0001), while less powerful determinants were 24 h, daily and nightly SBP (p = 0.02, p = 0.002, p = 0.004 respectively).
CONCLUSIONS:
Older sarcopenic and physically frail patients showed LVH with a tendency towards concentric geometry. The main determinant of LVM was SBP, highlighting the key role that hemodynamic condition plays in determining LVH in this population.
Copyright © 2021 Elsevier Inc. All rights reserved.
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Cigarette smoke exposure causes systemic and autonomic cardiocirculatory changes in rats depending on the daily exposure dose.
Life Sci2021 Apr;():119498. doi: S0024-3205(21)00483-5.
Miguel João Paulo, Dias Andressa Cunha, Bettini Nathalia Rodrigues, de Souza Samuel Antônio Biagio Armânio, Durão Marília Pereira Lima, de Castro Oliveira Lucas Vaz, Monedeiro Fernanda, Ramalho Leandra Naira Zambelli, Branco Luiz Guilherme S, Sabino João Paulo Jacob, de Toledo Durand Marina,
Abstract
AIMS:
To evaluate the systemic changes and autonomic cardiocirculatory control of awaken rats chronically exposed to the cigarette smoke (CS) of 1 or 2 cigarettes/day.
MAIN METHODS:
Rats were exposed to clean air (control) or cigarette smoke of 1 (CS1) or 2 (CS2) cigarettes/animal/day for 30?days. Then, arterial pressure (AP) and heart rate (HR) were recorded in conscious rats to assess spontaneous baroreflex sensitivity and HR and AP variabilities. Evoked baroreflex and cardiac autonomic tone were evaluated by vasoactive drugs and autonomic blockers, respectively. In another group, ventilatory and cardiovascular parameters were recorded under hypoxia and hypercapnia stimulus. At the end of protocols, heart, lung, kidneys and liver were collected for histological analysis.
KEY FINDINGS:
Rats exposed to CS showed morphological changes, being more evident in the CS2 group. Also, less weight gain and cardiac hypertrophy were prominent in CS2 rats. Basal AP and HR, spontaneous baroreflex sensitivity and cardiovascular variabilities were similar among groups. CS exposure progressively blunted the bradycardia response to phenylephrine (-2.2?±?0.1 vs. -1.7?±?0.2 vs. -1.5?±?0.2) while the tachycardia response to sodium nitroprusside was slightly increased compared to control. Vagal tone was not affected by CS, but CS2 rats exhibited higher sympathetic tone (-25?±?4 vs. -28?±?4 vs. -56?±?9) and lower intrinsic HR (411?±?4 vs. 420?±?8 vs. 390?±?6). Exposure to CS of 2 cigarettes also exacerbated the reflex cardiovascular and ventilatory responses to hypoxia and hypercapnia.
SIGNIFICANCE:
CS exposure for 30?days promoted systemic changes and autonomic cardiocirculatory dysfunction in rats depending on the daily exposure dose.
Copyright © 2018. Published by Elsevier Inc.
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Hypertrophic cardiomyopathy considerations for the managed care pharmacist.
Am J Manag Care2021 Apr;27(6 Suppl):S118-S125. doi: 10.37765/ajmc.2021.88629.
Taddei-Allen Patty,
Abstract
Hypertrophic cardiomyopathy (HCM) is often seen in patients as an autosomal dominant genetic heart disease with a variable clinical course. It is characterized by left ventricular hypertrophy, and with some patients, there is no evidence of a genetic etiology or presence of HCM in family members. Young age at diagnosis and the presence of a pathogenic or likely pathogenic sarcomere variant predict greater lifelong risk for stroke, heart failure, ventricular arrhythmia, atrial fibrillation, or mortality. Most individuals affected with HCM live to an average lifespan due to improvements in earlier diagnosis, sudden cardiac death risk stratification, family screening, pharmacologic therapy, devices, and invasive septal reduction therapy. Although these interventions have improved mortality, they are associated with significant costs and morbidities. There are burdensome costs related to genetic testing, family screening, implantable cardioverter-defibrillators, alcohol septal ablation, septal myectomy, pacemaker placement, and cardiac transplantation. In addition to these economic considerations, patients with HCM may experience a diminished health-related quality of life. Shared decision making between the patient and physician, use of multidisciplinary teams at HCM centers, and judicious use of exercise when appropriate have been shown to improve patient outcomes. Currently, treatments for HCM do not treat the underlying illness. Although not yet approved by the FDA, cardiac myosin inhibitors have recently shown promise in clinical trials to treat the underlying pathology of HCM. If approved by the FDA, managed care pharmacists should be ready to assess their safety and efficacy to improve the clinical burden and quality of life of those affected by HCM and reduce medical costs for these patients against standard of care. Long-term safety and efficacy data showing reductions in hospitalizations, morbidity, and mortality will be needed to determine their actual utility in managing HCM and ultimate place in therapy.
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Hypertrophic cardiomyopathy: diagnosis and therapeutic options.
Am J Manag Care2021 Apr;27(6 Suppl):S111-S117. doi: 10.37765/ajmc.2021.88628.
Gluckman Ty J,
Abstract
Hypertrophic cardiomyopathy is an underdiagnosed genetic disorder, resulting from mutations in sarcomeric proteins. It has a highly variable clinical presentation, with some individuals remaining asymptomatic and others having significant limitation of functional status. The disorder is typically characterized by left ventricular hypertrophy that is not explained by another cause. Patients are further classified based on whether there is obstruction of the left ventricular outflow tract. To-date, there are no pharmacologic therapies that alter the natural history of the disease. Therapeutic approaches have instead focused on symptom relief and prevention of sudden cardiac death. Newer therapies under investigation represent potential means to improve limiting symptoms.
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Deficiency in Nebulin Repeats of Sarcomeric Nebulette is Detrimental for Cardiomyocyte Tolerance to Exercise and Biomechanical Stress.
Am J Physiol Heart Circ Physiol2021 Apr;():. doi: 10.1152/ajpheart.00732.2020.
Vejandla Ramona M, Orgil Buyan-Ochir, Alberson Neely R, Li Ning, Munkhsaikhan Undral, Khuchua Zaza, Martherus Ruben, Azeloglu Evren U, Xu Fuyi, Lu Lu, Towbin Jeffrey A, Purevjav Enkhsaikhan,
Abstract
BACKGROUND:
The actin-binding sarcomeric nebulette (NEBL) protein provides efficient contractile flexibility via interaction with desmin intermediate filaments. NEBL gene mutations affecting the nebulin repeat (NR) domain is known to induce cardiomyopathy.
OBJECTIVE:
The study aimed to explore the roles of NEBL in exercise and biomechanical stress response.
METHODS:
We ablated exon3 encoding the first NR of Nebl and created global Nebl knockout mice. Cardiac function, structure and transcriptome was assessed before and after a 4-week treadmill regimen. A Nebl-based exercise signaling network was constructed using systems genetics methods. H9C2 and neonatal rat cardiomyocytes (NRCs) expressing wild-type or mutant NEBL underwent cyclic mechanical strain.
RESULTS:
Nebl mice demonstrated diastolic dysfunction with preserved systolic function at 6-months of age. After treadmill running, 4-month-old Nebl mice developed concentric cardiac hypertrophy and left ventricular dilation compared to running Nebl and sedentary Nebl mice. Disturbance of sarcomeric Z-disks and thin filaments architecture, disruption of intercalated disks and mitochondria were found in exercised Nebl mice. A Nebl-based exercise signaling network included Csrp3, Des, Fbox32, Jup, Myh6, and Myh7. Disturbed expression of TM1, DES, JUP, b-catenin, MLP, ?-actinin2 and vinculin proteins was demonstrated. In H9C2 cells, NEBL was recruited into focal adhesions at 24-hours post-strain and redistributed along with F-actin at 72-hours post-strain, suggesting time-dependent redistribution of NEBL in response to strain. NEBL mutations cause desmin disorganization in NRCs upon stretch.
CONCLUSIONS:
Upon stretch, NEBL deficiency causes disturbed sarcomere, Z-disks and desmin organization, and prevents NEBL redistribution to focal adhesions in cardiomyocytes, weakening cardiac tolerance to stress.
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