The Microenvironment of the Pathogenesis of Cardiac Hypertrophy

Bazgir, Farhad; Nau, Julia; Nakhaei‐Rad, Saeideh; Amin, Ehsan; Wolf, Matthew J.; Saucerman, Jeffrey J.; Lorenz, Kristina; Ahmadian, Mohammad Réza

doi:10.3390/cells12131780

Cited by 15 publications

(8 citation statements)

References 340 publications

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“…The factors that determine these divergent trends in ACE2 protein expression in cardiomyocytes and non-cardiomyocytes are unclear. However, it is most likely associated with myocardial remodeling characteristics, where the capillary network becomes inadequate during the hypertrophy of cardiomyocytes [51,52]. This could be supported by a significant negative correlation between the ACE2 immunostaining score in non-cardiomyocytes and the left ventricular mass documented in our study.…”

Section: Discussionsupporting

confidence: 71%

Myocardial Angiotensin-Converting Enzyme 2 Protein Expression in Ischemic Heart Failure

Siratavičiūtė,

Pangonytė,

Utkienė

et al. 2023

IJMS

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The angiotensin-converting enzyme 2 (ACE2)-angiotensin-(1-7)-Mas receptor axis plays a significant role in regulating myocardial remodeling and the development of heart failure (HF), with ACE2 being the primary focus. However, contemporary understanding of the membrane-bound form of the human ACE2 protein remains insufficient. The purpose of this study was to determine the expression of ACE2 protein in different cells of the left ventricular myocardium in non-diseased hearts and at various stages of ischemic HF. A total of 103 myocardial tissue samples from the left ventricle underwent quantitative and semi-quantitative immunohistochemical analysis. Upon assessing ACE2 immunostaining in all myocardial cells through unselective digital image analysis, there was no change in the stage A HF group. Nevertheless, the expression of ACE2 membrane protein in cardiomyocytes showed a tendency to increase, while non-cardiomyocyte ACE2 expression decreased significantly (p < 0.001). In the stage B HF group, the intensity of ACE2 immunostaining continued to increase with rising cardiomyocyte ACE2 expression (p < 0.001). Non-cardiomyocyte expression, in contrast, remained similar to that observed in the stage A HF group. In the stages C/D HF group, ACE2 expression reached its highest level in cardiomyocytes (p < 0.001), while ACE2 expression in non-cardiomyocytes was the lowest (p < 0.001). These changes in ACE2 protein levels are associated with left ventricular remodeling in ischemic HF.

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Section: Discussionsupporting

confidence: 71%

Myocardial Angiotensin-Converting Enzyme 2 Protein Expression in Ischemic Heart Failure

Siratavičiūtė,

Pangonytė,

Utkienė

et al. 2023

IJMS

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“…Due to haemodynamic overload and subsequent mechanical stress, mostly cardiomyocytes, but other cardiac cell types also, release autocrine and paracrine factors such as hormones, cytokines, growth factors (GFs), and chemokines. These factors, that may be meant to contribute to the adaptation to stress, when sustained, become maladaptive mediators contributing to decompensation to heart failure (reviewed in 58 , 59 ).…”

Section: Non-cardiomyocyte Eventsmentioning

confidence: 99%

Large animal models of pressure overload-induced cardiac left ventricular hypertrophy to study remodelling of the human heart with aortic stenosis

Beslika,

Leite-Moreira,

De Windt

et al. 2024

Cardiovascular Research

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Pathologic cardiac hypertrophy is a common consequence of many cardiovascular diseases, including aortic stenosis. Aortic stenosis is known to increase the pressure load of the left ventricle, causing a compensative response of the cardiac muscle, which progressively will lead to dilation and heart failure. In a cellular level, this corresponds to a considerable increase in the size of cardiomyocytes, named cardiomyocyte hypertrophy, as their proliferation capacity is attenuated upon the first developmental stages. Cardiomyocytes, in order to cope with the increased workload (overload), suffer alterations in their morphology, nuclear content, energy metabolism, intracellular homeostatic mechanisms, contractile activity and cell death mechanisms. Moreover, modifications in the cardiomyocyte niche, involving inflammation, immune infiltration, fibrosis and angiogenesis, contribute to the subsequent events of a pathologic hypertrophic response. Considering the emerging need for a better understanding of the condition and treatment improvement, as the only available treatment option of aortic stenosis consists of surgical interventions at a late stage of the disease, when the cardiac muscle state is irreversible, large animal models have been developed to mimic the human condition, to the greatest extend. Smaller animal models lack physiology and cellular and molecular mechanisms that sufficiently resemblance humans; in vitro techniques yet fail to provide adequate complexity. Animals, such as the ferret (Mustello purtorius furo), lapine (rabbit, Oryctolagus cunigulus), feline (cat, Felis catus), canine (dog, Canis lupus familiaris), ovine (sheep, Ovis aries) and porcine (pig, Sus scrofa), have contributed to the research by elucidating implicated cellular and molecular mechanisms of the condition. Essential discoveries of each model are reported and discussed briefly in this review. Results of large animal experimentation could further be interpreted aiming to the prevention of the disease progress or, alternatively, to the regression of the implicated pathologic mechanisms to a physiologic state. This review summarizes the important aspects of the pathophysiology of LV hypertrophy and the applied surgical large animal models that better mimic the condition until the present moment.

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“…At the same time, the immune response is one of the important reasons for the development of HCM. Numerous studies have shown that HCM patients have leukocyte infiltration and elevated levels of inflammatory cytokines in their myocardium, which may be key factors in the progression of HCM to the end stage of heart failure [ 7 ]. In addition, the genetic deficiency of the key inflammatory cytokine IL-6 has been shown to alleviate TAC-induced left ventricular dysfunction and hypertrophy [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic Analyses and Experimental Validation Identified Immune-Related lncRNA–mRNA Pair MIR210HG–BPIFC Regulating the Progression of Hypertrophic Cardiomyopathy

Zhang,

Zhao,

Jin

et al. 2024

IJMS

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Hypertrophic cardiomyopathy (HCM) is a disease in which the myocardium of the heart becomes asymmetrically thickened, malformed, disordered, and loses its normal structure and function. Recent studies have demonstrated the significant involvement of inflammatory responses in HCM. However, the precise role of immune-related long non-coding RNAs (lncRNAs) in the pathogenesis of HCM remains unclear. In this study, we performed a comprehensive analysis of immune-related lncRNAs in HCM. First, transcriptomic RNA-Seq data from both HCM patients and healthy individuals (GSE180313) were reanalyzed thoroughly. Key HCM-related modules were identified using weighted gene co-expression network analysis (WGCNA). A screening for immune-related lncRNAs was conducted within the key modules using immune-related mRNA co-expression analysis. Based on lncRNA–mRNA pairs that exhibit shared regulatory microRNAs (miRNAs), we constructed a competing endogenous RNA (ceRNA) network, comprising 9 lncRNAs and 17 mRNAs that were significantly correlated. Among the 26 lncRNA–mRNA pairs, only the MIR210HG–BPIFC pair was verified by another HCM dataset (GSE130036) and the isoprenaline (ISO)-induced HCM cell model. Furthermore, knockdown of MIR210HG increased the regulatory miRNAs and decreased the mRNA expression of BPIFC correspondingly in AC16 cells. Additionally, the analysis of immune cell infiltration indicated that the MIR210HG–BPIFC pair was potentially involved in the infiltration of naïve CD4+ T cells and CD8+ T cells. Together, our findings indicate that the decreased expression of the lncRNA–mRNA pair MIR210HG–BPIFC was significantly correlated with the pathogenesis of the disease and may be involved in the immune cell infiltration in the mechanism of HCM.

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The Microenvironment of the Pathogenesis of Cardiac Hypertrophy

Cited by 15 publications

References 340 publications

Myocardial Angiotensin-Converting Enzyme 2 Protein Expression in Ischemic Heart Failure

Myocardial Angiotensin-Converting Enzyme 2 Protein Expression in Ischemic Heart Failure

Large animal models of pressure overload-induced cardiac left ventricular hypertrophy to study remodelling of the human heart with aortic stenosis

Transcriptomic Analyses and Experimental Validation Identified Immune-Related lncRNA–mRNA Pair MIR210HG–BPIFC Regulating the Progression of Hypertrophic Cardiomyopathy

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