DONA ORA
Pubblicazioni recenti - cardiac hypertrophy
-
DNA Vaccine Treatment in Dogs Experimentally Infected with .
J Immunol Res2020 ;2020():9794575. doi: 10.1155/2020/9794575.
Arce-Fonseca Minerva, Carbajal-Hernández Ana C, Lozano-Camacho Mónica, Carrillo-Sánchez Silvia Del C, Roldán Francisco-Javier, Aranda-Fraustro Alberto, Rosales-Encina José Luis, Rodríguez-Morales Olivia,
Abstract
Chagas disease is a chronic and potentially lethal disorder caused by the parasite , and an effective treatment has not been developed for chronic Chagas disease. The objective of this study was to determine the effectiveness of a therapeutic DNA vaccine containing genes in dogs with experimentally induced Chagas disease through clinical, pathological, and immunological analyses. Infection of Beagle dogs with the H8 strain was performed intraperitoneally with 3500 metacyclic trypomastigotes/kg body weight. Two weeks after infection, plasmid DNA immunotherapy was administered thrice at 15-day intervals. The clinical (physical and cabinet studies), immunological (antibody and cytokine profiles and lymphoproliferation), and macro- and microscopic pathological findings were described. A significant increase in IgG and cell proliferation was recorded after immunotherapy, and the highest stimulation index (3.02) was observed in dogs treated with the pBCSSP4 plasmid. The second treatment with both plasmids induced an increase in IL-1, and the third treatment with the pBCSSP4 plasmid induced an increase in IL-6. The pBCSP plasmid had a good Th1 response regulated by high levels of IFN-gamma and TNF-alpha, whereas the combination of the two plasmids did not have a synergistic effect. Electrocardiographic studies registered lower abnormalities and the lowest number of individuals with abnormalities in each group treated with the therapeutic vaccine. Echocardiograms showed that the pBCSSP4 plasmid immunotherapy preserved cardiac structure and function to a greater extent and prevented cardiomegaly. The two plasmids alone controlled the infection moderately by a reduction in the inflammatory infiltrates in heart tissue. The immunotherapy was able to reduce the magnitude of cardiac lesions and modulate the cellular immune response; the pBCSP treatment showed a clear Th1 response; and pBCSSP4 induced a balanced Th1/Th2 immune response that prevented severe cardiac involvement. The pBCSSP4 plasmid had a better effect on most of the parameters evaluated in this study; therefore, this plasmid can be considered an optional treatment against Chagas disease in naturally infected dogs.
Copyright © 2020 Minerva Arce-Fonseca et al.
Guarda su PubMed
-
Plasma Homocysteine and Cardiovascular Organ Damage in a Population with a High Prevalence of Risk Factors.
J Clin Endocrinol Metab2020 May;():. doi: dgaa289.
Kozakova Michaela, Morizzo Carmela, Penno Giuseppe, Shore Angela C, Nilsson Jan, Palombo Carlo,
Abstract
PURPOSE:
It is unclear whether plasma homocysteine (Hcy) has a direct noxious impact on cardiovascular (CV) system or whether its association with cardiovascular events (CVE) is mediated by established risk factors. To explore the role of Hcy in CV impairment, the study evaluated cross-sectional relationships between plasma Hcy and indices of CV organ damage together with the associations of these indices with the history of CVE.
METHODS:
In 269 patients with a high prevalence of diabetes, dyslipidemia and hypertension were measured carotid intima-media thickness, ankle-brachial index (ABI), reactive hyperemic index, carotid-femoral pulse-wave velocity (cfPWV), left ventricular (LV) mass and cardiac index.
RESULTS:
132 patients had carotid plaque, 31 ABI<0.90, 126 endothelial dysfunction, 66 increased cfPWV, 125 LV hypertrophy (LVH), 153 decreased cardiac index and 115 history of CVE. Plasma Hcy levels were related to LV mass and ABI, after adjustment for covariates and creatinine. Significantly higher Hcy levels were found in patients with LVH (8.5[4.4] vs 7.6[2.8] ?mol/L; adjusted P=0.001) and ABI<0.9 (10.4[3.8] vs 7.9[3.4] ?mol/L; adjusted P=0.001), when compared to those with LV mass and ABI within limits. Hcy levels were comparable between patients with and without carotid plaques, increased arterial stiffness, impaired endothelial and LV pump function. Within markers of CV organ damage, only LVH was associated with history of CVE.
CONCLUSION:
This study demonstrated an independent association between Hcy and LV mass as well as between LVH and a history of CVE and suggests that LVH may represent one of the pathophysiologic links between Hcy and CV risk.
© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Guarda su PubMed
-
Microvascular and lymphatic dysfunction in HFpEF and its associated comorbidities.
Basic Res Cardiol2020 May;115(4):39. doi: 10.1007/s00395-020-0798-y.
Cuijpers Ilona, Simmonds Steven J, van Bilsen Marc, Czarnowska El?bieta, González Miqueo Arantxa, Heymans Stephane, Kuhn Annika R, Mulder Paul, Ratajska Anna, Jones Elizabeth A V, Brakenhielm Ebba,
Abstract
Heart failure with preserved ejection fraction (HFpEF) is a complex heterogeneous disease for which our pathophysiological understanding is still limited and specific prevention and treatment strategies are lacking. HFpEF is characterised by diastolic dysfunction and cardiac remodelling (fibrosis, inflammation, and hypertrophy). Recently, microvascular dysfunction and chronic low-grade inflammation have been proposed to participate in HFpEF development. Furthermore, several recent studies demonstrated the occurrence of generalized lymphatic dysfunction in experimental models of risk factors for HFpEF, including obesity, hypercholesterolaemia, type 2 diabetes mellitus (T2DM), hypertension, and aging. Here, we review the evidence for a combined role of coronary (micro)vascular dysfunction and lymphatic vessel alterations in mediating key pathological steps in HFpEF, including reduced cardiac perfusion, chronic low-grade inflammation, and myocardial oedema, and their impact on cardiac metabolic alterations (oxygen and nutrient supply/demand imbalance), fibrosis, and cardiomyocyte stiffness. We focus primarily on HFpEF caused by metabolic risk factors, such as obesity, T2DM, hypertension, and aging.
Guarda su PubMed
-
Mutations in cause an autosomal-recessive form of hypertrophic cardiomyopathy.
Heart2020 May;():. doi: heartjnl-2020-316913.
Salazar-Mendiguchía Joel, Ochoa Juan Pablo, Palomino-Doza Julian, Domínguez Fernando, Díez-López Carles, Akhtar Mohammed, Ramiro-León Soraya, Clemente María M, Pérez-Cejas Antonia, Robledo María, Gómez-Díaz Iria, Peña-Peña María Luisa, Climent Vicente, Salmerón-Martínez Francisco, Hernández Celestino, García-Granja Pablo E, Mogollón M Victoria, Cárdenas-Reyes Ivonne, Cicerchia Marcos, García-Giustiniani Diego, Lamounier Arsonval, Gil-Fournier Belén, Díaz-Flores Felícitas, Salguero Rafael, Santomé Luis, Syrris Petros, Olivé Montse, García-Pavía Pablo, Ortiz-Genga Martín, Elliott Perry M, Monserrat Lorenzo, ,
Abstract
OBJECTIVE:
Up to 50% of patients with hypertrophic cardiomyopathy (HCM) show no disease-causing variants in genetic studies. has been suggested as a candidate gene for the development of cardiomyopathies, although evidence for a causative role in HCM is limited. We sought to investigate the relationship between rare variants in and the development of HCM.
METHODS:
was sequenced by next generation sequencing in 4867 index cases with a clinical diagnosis of HCM and in 3628 probands with other cardiomyopathies. Additionally, 3136 index cases with familial cardiovascular diseases other than cardiomyopathy (mainly channelopathies and aortic diseases) were used as controls.
RESULTS:
Sixteen index cases with rare homozygous or compound heterozygous variants in (15 HCM and one restrictive cardiomyopathy) were included. No homozygous or compound heterozygous were identified in the control population. Familial evaluation showed that only homozygous and compound heterozygous had signs of disease, whereas all heterozygous family members were healthy. The mean age at diagnosis was 35 years (range 15-69). Fifty per cent of patients had concentric left ventricular hypertrophy (LVH) and 45% were asymptomatic at the moment of the first examination. Significant degrees of late gadolinium enhancement were detected in 80% of affected individuals, and 20% of patients had left ventricular (LV) systolic dysfunction. Fifty per cent had non-sustained ventricular tachycardia. Twenty per cent of patients suffered an adverse cerebrovascular event (20%).
CONCLUSION:
appears to be an uncommon cause of HCM inherited in an autosomal-recessive manner and associated with concentric LVH and a high rate of LV dysfunction.
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Guarda su PubMed
-
Whole-genome DNA sequencing: The key to detecting a sarcomeric mutation in a 'false genotype-negative' family with hypertrophic cardiomyopathy.
Rev Port Cardiol2020 May;():. doi: S0870-2551(20)30153-0.
Gomes Ana Catarina, Barbosa Pedro Santos, Coutinho Ana, Cruz Inês, Carmo-Fonseca Maria, Lopes Luís Rocha,
Abstract
The authors report the clinical and genetic investigation of a family with hypertrophic cardiomyopathy (HCM). The individuals described are three affected first-degree relatives (father, daughter and son), one affected niece and unaffected nephew and niece. Those affected all share a very similar phenotype consisting of asymmetric HCM, with hypertrophy particularly affecting the septum and the anterior wall, and similar electrocardiographic features, including a short PR interval. Case 1 (proband) presented with obstructive HCM and had undergone myectomy and mitral valve replacement. Case 2 (oldest offspring of Case 1) had non-obstructive HCM with exertional angina and NYHA II heart failure (HF) symptoms; she developed non-sustained ventricular tachycardia during follow-up and received a single-chamber ICD for primary prevention of sudden cardiac death. Case 3 (son of case 1) presented with asymptomatic non-obstructive HCM and developed NYHA II HF symptoms during follow-up. Case 4 had non-obstructive HCM, mainly with NYHA II HF symptoms. Testing of the proband for sarcomeric mutations and phenocopies was initially negative. After eight years of clinical follow-up, the suspicion of an undiscovered pathogenic gene mutation shared among the members of this family led us to enroll the proband in a whole-genome sequencing research project, which revealed a heterozygous pathogenic intronic MYBPC3 variant (c.1227-13G>A [rs397515893]), cosegregating with the phenotype.
Copyright © 2020 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.
Guarda su PubMed
-
Correction to: Metformin Improves Cardiac Metabolism and Function, and Prevents Left Ventricular Hypertrophy in Spontaneously Hypertensive Rats.
J Am Heart Assoc -
Cardioprotective effects of melatonin: Focusing on its roles against diabetic cardiomyopathy.
Biomed Pharmacother2020 May;128():110260. doi: S0753-3322(20)30452-2.
Song Yan-Jun, Zhong Chong-Bin, Wu Wei,
Abstract
Melatonin is a pineal-produced indole known for its anti-aging, antiapoptotic and antioxidant properties. In past decades, the protective potentials of melatonin for cardiovascular diseases, such as atherosclerosis and myocardial infarction, have been widely revealed, triggering more investigations focused on other cardioprotective effects of melatonin. Recently, the roles of melatonin in diabetic cardiomyopathy (DCM) have attracted increased attention. In this regard, researchers found that melatonin attenuated cardiac fibrosis and hypertrophy, thus interrupting the development of DCM. Retinoid-related orphan receptor ? is a key melatonin receptor that contributed to the cardioprotective effect of melatonin in hearts with DCM. For the downstream mechanisms, the inhibition of mammalian STE20-like kinase 1 plays a pivotal role, which exerts antiapoptotic and proautophagic effects, thus enhancing cardiac tolerance in high-glucose conditions. In addition, other signalling mechanisms, such as sirtuin-1/peroxisome proliferator-activated receptor gamma-coactivator alpha and endoplasmic reticulum-related signalling, are also involved in the protective effects of melatonin on cardiomyocytes under diabetic conditions. This review will focus on the protective signalling mechanisms regulated by melatonin and provide a better understanding of the therapeutic applications of melatonin signalling in DCM.
Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
Guarda su PubMed
-
Early Growth Patterns and Cardiac Structure and Function at Midlife: Northern Finland 1966 Birth Cohort Study.
J Pediatr2020 Jun;221():151-158.e1. doi: S0022-3476(20)30327-9.
Korpela Nelli, Kaikkonen Kari, Auvinen Juha, Tulppo Mikko P, Junttila Juhani, Perkiömäki Juha, Järvelin Marjo-Riitta, Huikuri Heikki V, Kiviniemi Antti M,
Abstract
OBJECTIVES:
To evaluate the influence of early growth patterns that have previously been associated with later cardiometabolic risk on cardiac left ventricular (LV) structure and function in midlife.
STUDY DESIGN:
A subpopulation of the Northern Finland Birth Cohort 1966 took part in follow-up, including echocardiography (n = 1155) at the age of 46 years. Body mass index (BMI) growth curves were modeled based on frequent anthropometric measurements in childhood. Age and BMI at adiposity peak (n = 482, mean age 9.0 months) and at adiposity rebound (n = 586, mean age 5.8 years) were determined. Results are reported as unstandardized beta (?) or OR with 95% CIs for 1 SD increase in early growth variable.
RESULTS:
Earlier adiposity rebound was associated with increased LV mass index (? = -4.10 g/m (-6.9, -1.3); P = .004) and LV end-diastolic volume index (? = -2.36 mL/m (-3.9, -0.84); P = .002) as well as with eccentric LV hypertrophy (OR 0.54 [0.38, 0.77]; P = .001) in adulthood in males. BMI at adiposity rebound was directly associated with LV mass index (? = 2.33 g/m [0.80, 3.9]; P = .003). Higher BMI at both adiposity peak and at adiposity rebound were associated with greater LV end-diastolic volume index (? = 1.47 mL/m; [0.51, 2.4], ? = 1.28 mL/m [0.41, 2.2], respectively) and also with eccentric LV hypertrophy (OR 1.41 [1.10, 1.82], OR 1.53 [1.23, 1.91], respectively) and LV concentric remodeling (OR 1.38 [1.02, 1.87], OR 1.40 [1.06, 1.83], respectively) in adulthood (P < .05 for all). These relationships were only partly mediated by adult BMI.
CONCLUSIONS:
Early growth patterns in infancy and childhood contribute to cardiac structure at midlife.
Copyright © 2020 Elsevier Inc. All rights reserved.
Guarda su PubMed
-
Pulse-cancellation echocardiography in Fabry disease diagnosis.
Echocardiography2020 May;():. doi: 10.1111/echo.14707.
Joye Evan, Zheng Wen Qian, Torosoff Mikhail,
Abstract
Pulse-cancellation imaging is a novel echocardiographic imaging modality developed for detection of myocardial fibrosis. This technique cancels echocardiographic reflections from the normal myocardium but clearly displays the abnormal tissue. We describe, for the first time, pulse-cancellation echocardiography application in detecting Fabry disease myocardial involvement. We present the case where both pulse-cancellation imaging and cardiac MRI concurrently revealed myocardial deposits in a patient with genotypically confirmed Fabry disease.
© 2020 Wiley Periodicals LLC.
Guarda su PubMed
-
Nuclear-mitochondrial communication involving miR-181c plays an important role in cardiac dysfunction during obesity.
J Mol Cell Cardiol2020 May;():. doi: S0022-2828(20)30191-7.
Roman Barbara, Kaur Pawandeep, Ashok Deepthi, Kohr Mark, Biswas Roopa, O'Rourke Brian, Steenbergen Charles, Das Samarjit,
Abstract
AIMS:
In cardiomyocytes, there is microRNA (miR) in the mitochondria that originates from the nuclear genome and matures in the cytoplasm before translocating into the mitochondria. Overexpression of one such miR, miR-181c, can lead to heart failure by stimulating reactive oxygen species (ROS) production and increasing mitochondrial calcium level ([Ca]). Mitochondrial calcium uptake 1 protein (MICU1), a regulatory protein in the mitochondrial calcium uniporter complex, plays an important role in regulating [Ca]. Obesity results in miR-181c overexpression and a decrease in MICU1. We hypothesize that lowering miR-181c would protect against obesity-induced cardiac dysfunction.
METHODS AND RESULTS:
We used an in vivo mouse model of high-fat diet (HFD) for 18?weeks and induced high lipid load in H9c2 cells with oleate-conjugated bovine serum albumin in vitro. We tested the cardioprotective role of lowering miR-181c by using miR-181c/d mice (in vivo) and AntagomiR against miR-181c (in vitro). HFD significantly upregulated heart levels of miR-181c and led to cardiac hypertrophy in wild-type mice, but not in miR-181c/d mice. HFD also increased in ROS production and pyruvate dehydrogenase activity (a surrogate for [Ca]), but the increases were alleviated in miR-181c/d mice. Moreover, miR-181c/d mice fed a HFD had higher levels of MICU1 than did wild-type mice fed a HFD, attenuating the rise in [Ca]. Overexpression of miR-181c in neonatal ventricular cardiomyocytes (NMVM) caused increased ROS production, which oxidized transcription factor Sp1 and led to a loss of Sp1, thereby slowing MICU1 transcription. Hence, miR-181c increases [Ca] through Sp1 oxidation and downregulation of MICU1, suggesting that the cardioprotective effect of miR-181c/d results from inhibition of Sp1 oxidation.
CONCLUSION:
This study has identified a unique nuclear-mitochondrial communication mechanism in the heart orchestrated by miR-181c. Obesity-induced overexpression of miR-181c increases [Ca] via downregulation of MICU1 and leads to cardiac injury. A strategy to inhibit miR-181c in cardiomyocytes can preserve cardiac function during obesity by improving mitochondrial function. Altering miR-181c expression may provide a pharmacologic approach to improve cardiomyopathy in individuals with obesity/type 2 diabetes.
Copyright © 2019. Published by Elsevier Ltd.
Guarda su PubMed
-
Exercise training reverses cardiac aging phenotypes associated with heart failure with preserved ejection fraction in male mice.
Aging Cell2020 May;():e13159. doi: 10.1111/acel.13159.
Roh Jason D, Houstis Nicholas, Yu Andy, Chang Bliss, Yeri Ashish, Li Haobo, Hobson Ryan, Lerchenmüller Carolin, Vujic Ana, Chaudhari Vinita, Damilano Federico, Platt Colin, Zlotoff Daniel, Lee Richard T, Shah Ravi, Jerosch-Herold Michael, Rosenzweig Anthony,
Abstract
Heart failure with preserved ejection fraction (HFpEF) is the most common type of HF in older adults. Although no pharmacological therapy has yet improved survival in HFpEF, exercise training (ExT) has emerged as the most effective intervention to improving functional outcomes in this age-related disease. The molecular mechanisms by which ExT induces its beneficial effects in HFpEF, however, remain largely unknown. Given the strong association between aging and HFpEF, we hypothesized that ExT might reverse cardiac aging phenotypes that contribute to HFpEF pathophysiology and additionally provide a platform for novel mechanistic and therapeutic discovery. Here, we show that aged (24-30 months) C57BL/6 male mice recapitulate many of the hallmark features of HFpEF, including preserved left ventricular ejection fraction, subclinical systolic dysfunction, diastolic dysfunction, impaired cardiac reserves, exercise intolerance, and pathologic cardiac hypertrophy. Similar to older humans, ExT in old mice improved exercise capacity, diastolic function, and contractile reserves, while reducing pulmonary congestion. Interestingly, RNAseq of explanted hearts showed that ExT did not significantly modulate biological pathways targeted by conventional HF medications. However, it reversed multiple age-related pathways, including the global downregulation of cell cycle pathways seen in aged hearts, which was associated with increased capillary density, but no effects on cardiac mass or fibrosis. Taken together, these data demonstrate that the aged C57BL/6 male mouse is a valuable model for studying the role of aging biology in HFpEF pathophysiology, and provide a molecular framework for how ExT potentially reverses cardiac aging phenotypes in HFpEF.
© 2020 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
Guarda su PubMed
-
MicroRNA-27 attenuates pressure overload-Induced cardiac hypertrophy and dysfunction by targeting galectin-3.
Arch Biochem Biophys2020 May;():108405. doi: S0003-9861(20)30414-8.
Zhang Meiqi, Cheng Kang, Chen Huan, Tu Jianfeng, Shen Ye, Pang Lingxiao, Wu Weihua,
Abstract
Cardiac hypertrophy is an adaptive response to hemodynamic stress to compensate for cardiac dysfunction. MicroRNAs can regulate cardiac function and play a vital role in the regulation of cardiac hypertrophy. In the current study, in vivo and vitro hypertrophy models are established to explore the role of miR-27b and to elucidate the underlying mechanism in cardiac hypertrophy. Expression of miR-27b was down-regulated in mice with cardiac hypertrophy. The cardiac function of the mice with cardiac hypertrophy could be restored with the overexpression of miR-27b, this is observed in terms of decreasing LVEDd, LVESd, and increasing LVFS, LVEF. This study also predicted and confirmed that galectin-3 is a target gene of miR-27b. Depletion of galectin-3 significantly attenuated hypertrophy of hearts in both in vitro and in vivo tests. In conclusion, MiR-27b be used to exert a protective role against cardiac dysfunction and hypertrophy by decreasing the expression level of galectin-3. The methodology suggested in this study provides a novel therapeutic strategy against cardiac hypertrophy.
Copyright © 2020. Published by Elsevier Inc.
Guarda su PubMed
-
Cardiac Energetics in Patients with Aortic Stenosis and Preserved versus Reduced Ejection Fraction.
Circulation2020 May;():. doi: 10.1161/CIRCULATIONAHA.119.043450.
Peterzan Mark A, Clarke William T, Lygate Craig A, Lake Hannah A, Lau Justin Y C, Miller Jack J, Johnson Errin, Rayner Jennifer J, Hundertmark Moritz J, Sayeed Rana, Petrou Mario, Krasopoulos George, Srivastava Vivek, Neubauer Stefan, Rodgers Christopher, Rider Oliver J,
Abstract
Why some but not all patients with severe AS (SevAS) develop otherwise unexplained reduced systolic function is unclear. We investigate the hypothesis that reduced creatine kinase (CK) capacity and/or flux is associated with this transition. 102 participants were recruited to five groups: moderate AS (ModAS, n=13), severe AS, LVEF ?55% (SevAS-pEF, n=37), severe AS, LVEF<55% (SevAS-rEF, n=15), healthy volunteers with non-hypertrophied hearts with normal systolic function (NHv, n=30), and patients with non-hypertrophied, non-pressure loaded hearts with normal systolic function undergoing cardiac surgery and donating LV biopsy (NHbx, n=7). All underwent CMR imaging and P magnetic resonance spectroscopy (MRS) for myocardial energetics. LV biopsies (AS and NHBx) were analysed for; CK total activity, CK isoforms, citrate synthase (CS) activity and total creatine. Using serial block-face scanning electron microscopy, mitochondria-sarcomere diffusion distances were calculated. In the absence of failure, CK flux was lower in the presence of AS (by 32%, p=0.04), driven primarily by reduction in PCr/ATP (by 17%, p <0.001), with CK k unchanged (p=0.46),and is present in ModAS. Although lowest in the SevAS-rEF group, CK flux was not different to the SevAS-pEF group (p>0.99). Accompanying the fall in CK flux, total CK and CS activities, and absolute activities of MtCK and CK-MM were also lower (p<0.02, all analyses). Median mitochondria-sarcomere diffusion distances correlated well with CK total activity (r=0.86, p=.003). Total CK capacity is reduced in SevAS, with median values lowest in those with systolic failure, consistent with reduced energy supply reserve. Despite this, in vivo MRS measures of resting CK flux suggest that ATP delivery is reduced earlier, at the moderate AS stage, but where LV function remains preserved. These findings show that significant energetic impairment is already established in moderate AS, and suggest a fall in CK flux is not per se the cause of transition to systolic failure. However, as ATP demands increase with AS severity this could increase susceptibility to systolic failure. As such, targeting CK capacity and/or flux may be a therapeutic strategy to prevent/treat systolic failure in AS.
Guarda su PubMed
-
SP1-induced SNHG14 aggravates hypertrophic response in in vitro model of cardiac hypertrophy via up-regulation of PCDH17.
J Cell Mol Med2020 May;():. doi: 10.1111/jcmm.15073.
Long Yadong, Wang Lin, Li Zhiqiang,
Abstract
Cardiac hypertrophy (CH) is a common cardiac disease and is closely associated with heart failure. Protocadherin 17 (PCDH17) was reported to aggravate myocardial infarction. Present study was designed to illustrate the impact of PCDH17 and the mechanism of PCDH17 expression regulation in CH. CH model in vivo and in vitro was established by transverse aortic constriction (TAC) and Ang-II treatment. Hypertrophy was evaluated in PMC and H9c2 cells by examining cell surface area and hypertrophic markers. Results demonstrated that PCDH17 was up-regulated in CH in vivo and in vitro. PCDH17 knock-down alleviated hypertrophic response in Ang-II-induced cardiomyocytes. By means of ENCORI database and a series of mechanism assays, miR-322-5p and miR-384-5p were identified to interact with and inhibit PCDH17. Next, lncRNA SNHG14 (small nucleolar RNA host gene 14) was validated to sponge both miR-322-5p and miR-384-5p to elevate PCDH17 level. The subsequent rescue assays revealed that miR-322-5p and miR-384-5p restored SNHG14 depletion-mediated suppression on hypertrophy in Ang-II-induced cardiomyocytes. Besides, Sp1 transcription factor (SP1) was verified as the transcription factor activating both SNHG14 and PCDH17. Both SNHG14 and PCDH17 reversed SP1 knock-down-mediated repression on hypertrophy in Ang-II-induced cardiomyocytes. Together, present study first uncovered ceRNA network of SNHG14/miR-322-5p/miR-384-5p/PCDH17 in Ang-II-induced cardiomyocytes.
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
Guarda su PubMed
-
Cardiovascular Magnetic Resonance and Sport Cardiology: a Growing Role in Clinical Dilemmas.
J Cardiovasc Transl Res2020 May;():. doi: 10.1007/s12265-020-10022-7.
Maestrini Viviana, Torlasco Camilla, Hughes Rebecca, Moon James C,
Abstract
Exercise training induces morphological and functional cardiovascular adaptation known as the "athlete's heart" with changes including dilatation, hypertrophy, and increased stroke volume. These changes may overlap with pathological appearances. Distinguishing athletic cardiac remodelling from cardiomyopathy is important and is a frequent medical dilemma. Cardiac magnetic resonance (CMR) has a role in clinical care as it can refine discrimination of health from a disease where ECG and echocardiography alone have left or generated uncertainty. CMR can more precisely assess cardiac structure and function as well as characterise the myocardium detecting key changes including myocardial scar and diffuse fibrosis. In this review, we will review the role of CMR in sports cardiology.
Guarda su PubMed
-
The emerging spectrum of cardiopulmonary pathology of the coronavirus disease 2019 (COVID-19): Report of 3 autopsies from Houston, Texas, and review of autopsy findings from other United States cities.
Cardiovasc Pathol2020 May;48():107233. doi: S1054-8807(20)30037-5.
Buja Louis Maximilian, Wolf Dwayne A, Zhao Bihong, Akkanti Bindu, McDonald Michelle, Lelenwa Laura, Reilly Noah, Ottaviani Giulia, Elghetany M Tarek, Trujillo Daniel Ocazionez, Aisenberg Gabriel M, Madjid Mohammad, Kar Biswajit,
Abstract
This paper collates the pathological findings from initial published autopsy reports on 23 patients with coronavirus disease 2019 (COVID-19) from 5 centers in the United States of America, including 3 cases from Houston, Texas. Findings confirm that COVID-19 is a systemic disease with major involvement of the lungs and heart. Acute COVID-19 pneumonia has features of a distinctive acute interstitial pneumonia with a diffuse alveolar damage component, coupled with microvascular involvement with intra- and extravascular fibrin deposition and intravascular trapping of neutrophils, and, frequently, with formation of microthombi in arterioles. Major pulmonary thromboemboli with pulmonary infarcts and/or hemorrhage occurred in 5 of the 23 patients. Two of the Houston cases had interstitial pneumonia with diffuse alveolar damage pattern. One of the Houston cases had multiple bilateral segmental pulmonary thromboemboli with infarcts and hemorrhages coupled with, in nonhemorrhagic areas, a distinctive interstitial lymphocytic pneumonitis with intra-alveolar fibrin deposits and no hyaline membranes, possibly representing a transition form to acute fibrinous and organizing pneumonia. Multifocal acute injury of cardiac myocytes was frequently observed. Lymphocytic myocarditis was reported in 1 case. In addition to major pulmonary pathology, the 3 Houston cases had evidence of lymphocytic pericarditis, multifocal acute injury of cardiomyocytes without inflammatory cellular infiltrates, depletion of splenic white pulp, focal hepatocellular degeneration and rare glomerular capillary thrombosis. Each had evidence of chronic cardiac disease: hypertensive left ventricular hypertrophy (420 g heart), dilated cardiomyopathy (1070 g heart), and hypertrophic cardiomyopathy (670 g heart). All 3 subjects were obese (BMIs of 33.8, 51.65, and 35.2 Kg/m). Overall, the autopsy findings support the concept that the pathogenesis of severe COVID-19 disease involves direct viral-induced injury of multiple organs, including heart and lungs, coupled with the consequences of a procoagulant state with coagulopathy.
Copyright © 2020 Elsevier Inc. All rights reserved.
Guarda su PubMed
-
Administration of apo A-I (Milano) nanoparticles reverses pathological remodelling, cardiac dysfunction, and heart failure in a murine model of HFpEF associated with hypertension.
Sci Rep2020 May;10(1):8382. doi: 10.1038/s41598-020-65255-y.
Mishra Mudit, Muthuramu Ilayaraja, Kempen Herman, De Geest Bart,
Abstract
Therapeutic interventions with proven efficacy in heart failure with reduced ejection fraction (HFrEF) have been unsuccessful in heart failure with preserved ejection fraction (HFpEF). The modifiable risk factor with the greatest impact on the development of HFpEF is hypertension. The objectives of this study were to establish a murine model of HFpEF associated with hypertension and to evaluate the effect of apo A-I nanoparticles (MDCO-216) on established HFpEF in this model. Subcutaneous infusion of angiotensin II in combination with 1% NaCl in the drinking water was started at the age of 12 weeks in male C57BL/6?N mice and continued for the entire duration of the experiment. Treatment with MDCO-216 partially reversed established cardiac hypertrophy, cardiomyocyte hypertrophy, capillary rarefaction, and perivascular fibrosis in this model. Pressure-volume loop analysis was consistent with HFpEF in hypertension mice as evidenced by the preserved ejection fraction and a significant reduction of cardiac output (7.78?±?0.56?ml/min versus 10.5?±?0.7?ml/min; p?
Guarda su PubMed
-
Mibefradil alleviates high glucose-induced cardiac hypertrophy by inhibiting PI3K/Akt/mTOR-mediated autophagy.
J Cardiovasc Pharmacol2020 May;():. doi: 10.1097/FJC.0000000000000844.
Zhao Ling-Gong, Li Pei-Lin, Dai Ying, Deng Ji-Li, Shan Meng-Ya, Chen Bin, Zhang Ke-Bin, Guo Shao-Dong, Xu Zi-Hui,
Abstract
Cardiac hypertrophy causes heart failure and is associated with hyperglycemia in patients with diabetes mellitus (DM). Mibefradil, which acts as a T-type calcium channel blocker, exerts beneficial effects in patients with heart failure. In this study, we explored the effects and mechanism of mibefradil on high glucose-induced cardiac hypertrophy in H9c2 cells. H9c2 cells were incubated in high-glucose medium and then treated with different concentrations of mibefradil in the presence or absence of the Akt inhibitor MK2206 or mTOR inhibitor rapamycin. Cell size was evaluated via immunofluorescence, and mRNA expression of cardiac hypertrophy markers (ANP, BNP, and ?-MHC) was assessed by qRT-PCR. Changes in expression of p-PI3K, p-Akt, and p-mTOR were evaluated using western blotting, and autophagosome formation was detected by transmission electron microscopy. Our results indicate that mibefradil reduced the size of H9c2 cells, decreased mRNA expression of ANP, BNP, and ?-MHC, and decreased the level of autophagic flux. However, MK2206 and rapamycin induced autophagy and reversed the effects of mibefradil in high-glucose-induced H9c2 cells. In conclusion, mibefradil ameliorated high-glucose-induced cardiac hypertrophy by activating the PI3K/Akt/mTOR pathway and inhibiting excessive autophagy. Our study suggests that mibefradil can be used therapeutically to ameliorate cardiac hypertrophy in patients with DM.
Guarda su PubMed
-
IL-33 Induces Type-2-Cytokine Phenotype but Exacerbates Cardiac Remodeling Post-Myocardial Infarction with Eosinophil Recruitment, Worsened Systolic Dysfunction, and Ventricular Wall Rupture.
Clin Sci (Lond)2020 May;():. doi: CS20200402.
Ghali Rana, Habeichi Nada, Kaplan Abdullah, Tannous Cynthia, Abidi Emna, Bekdash Amira, Farhat Rima, Itani Hana, Jurjus Abdo, Booz George W, Mallat Ziad, Zouein Fouad A,
Abstract
Myocardial infarction (MI) is the leading cause of mortality worldwide. Interleukin-33 (IL-33) is a cytokine present in most cardiac cells and is secreted upon necrosis where it acts as a functional ligand for the ST2 receptor. Although IL-33/ST2 axis is protective against various forms of cardiovascular diseases, some studies suggest potential detrimental roles for IL-33 signaling. The aim of the present study was to examine the effect of IL-33 administration on cardiac function post-MI in mice. MI was induced by coronary artery ligation. Mice were treated with IL-33 (1µg/day) or vehicle for 4 and 7 days. Functional and molecular changes of the left ventricle (LV) were assessed. Single cell suspensions were obtained from bone marrow, heart, spleen, and peripheral blood to assess the immune cells using flow cytometry at 1, 3, and 7 days post-MI in IL-33 or vehicle-treated animals. The results of the present study suggest that IL-33 is effective in activating a type 2 cytokine milieu in the damaged heart, consistent with reduced early inflammatory and pro-fibrotic response. However, IL-33 administration was associated with worsened cardiac function and adverse cardiac remodeling in the MI mouse model. IL-33 administration increased infarct size, LV hypertrophy, cardiomyocyte death, and overall mortality rate due to cardiac rupture. Moreover, IL-33-treated MI mice displayed a significant myocardial eosinophil infiltration at 7 days post-MI when compared to vehicle-treated MI mice. This study reveals that although IL-33 administration is associated with a reparative phenotype following MI, it worsens cardiac remodeling and promotes heart failure.
Copyright 2020 The Author(s).
Guarda su PubMed
-
Prognostic significance of right ventricular hypertrophy and systolic function in Anderson-Fabry disease.
ESC Heart Fail2020 May;():. doi: 10.1002/ehf2.12712.
Graziani Francesca, Lillo Rosa, Panaioli Elena, Pieroni Maurizio, Camporeale Antonia, Verrecchia Elena, Sicignano Ludovico Luca, Manna Raffaele, Lombardo Antonella, Lanza Gaetano Antonio, Crea Filippo,
Abstract
AIMS:
Right ventricular hypertrophy (RVH) is a common finding in Anderson-Fabry disease (AFD), but the prognostic role of right ventricular (RV) involvement has never been assessed. The aim of our study was to evaluate the prognostic significance of RVH and RV systolic function in AFD.
METHODS AND RESULTS:
Forty-five AFD patients (56% male patients) with extensive baseline evaluation, including assessment of RVH and RV systolic function, were followed-up for an average of 51.2 ± 11.4 months. RV systolic function was assessed by standard and tissue Doppler echocardiography. Cardiovascular events were defined as new-onset atrial fibrillation (AF), sustained ventricular arrhythmias, heart failure, or pacemaker/implantable cardioverter defibrillator implantation; renal events were defined as progression to dialysis and/or renal transplantation or significant worsening of glomerular filtration rate; and cerebrovascular events were defined as transient ischaemic attack or stroke. Fourteen patients (31.1%) presented RVH, while RV systolic function was normal in all cases. During the follow-up period, 13 patients (28.8%, 11 male) experienced 18 major events, including two deaths. Cardiovascular events occurred in eight patients (17.7%). The most common event was pacemaker/implantable cardioverter defibrillator implantation (six patients, 13.3%), followed by AF (three cases, 6.6%). Only one case of worsening New York Heart Association class (from II to III and IV) was observed. Ischaemic stroke occurred in three cases (6.6%). Renal events were recorded in three patients (6.6%). At univariate analysis, several variables were associated with the occurrence of events, including RVH (HR: 7.09, 95% CI: 2.17 to 23.14, P = 0.001) and indexes of RV systolic function (tricuspid annular plane systolic excursion HR: 0.77, 95% CI: 0.62 to 0.96, P = 0.02; and RV tissue Doppler systolic velocity HR: 0.76, 95% CI: 0.61 to 0.93, P = 0.01). At multivariate analysis, proteinuria (HR:8.3, 95% CI: 2.88 to 23.87, P < 0.001) and left ventricular mass index (HR: 1.02, 95% CI: 1.00 to 1.03, P = 0.03) emerged as the only independent predictors of outcome.
CONCLUSIONS:
RVH and RV systolic function show significant association with clinical events in AFD, but only proteinuria and left ventricular mass index emerged as independent predictors of outcome. Our findings suggest that RV involvement does not influence prognosis in AFD and confirm that renal involvement and left ventricular hypertrophy are the main determinant of major cardiac and non-cardiac events.
© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.
Guarda su PubMed
