scholarly journals Molecular Mechanism of HSF1-Upregulated ALDH2 by PKC in Ameliorating Pressure Overload-Induced Heart Failure in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Endong Ji ◽  
Tiantian Jiao ◽  
Yunli Shen ◽  
Yunjia Xu ◽  
Yuanqing Sun ◽  
...  
Keyword(s):  
Heart Failure ◽  
Myocardial Hypertrophy ◽  
Pressure Overload ◽  
Mechanical Stretch ◽  
Compensatory Hypertrophy ◽  
Failure Model ◽  
Transverse Aortic Constriction ◽  
Aortic Constriction ◽  
Heart Failure Model

Evidences abound that HSF1 and ALDH2 are of cardioprotective effect, yet there is still no report on whether HSF1 can regulate ALDH2 to delay the occurrence of heart failure. We first established the pressure overload-induced heart failure model of mice by transverse aortic constriction (TAC) and discovered that, in the forming period of heart failure, changes of HSF1 and ALDH2 expression recorded the consistent trend. When HSF1 was upregulated/downregulated to delay/promote the occurrence of heart failure, PKC and ALDH2 also showed increased/decreased expression. And when ALDH2 was upregulated/downregulated, the role of HSF1 in delaying the occurrence of heart failure strengthened/weakened. Next, we used mechanical stretch to establish a pressure-stimulated myocardial hypertrophy model and discovered an increased expression of both HSF1 and ALDH2. When HSF1 was upregulated/downregulated to increase/decrease the expression of myocardial hypertrophy gene beta-MHC, PKC and ALDH2 recorded an increased/decreased expression. When an inhibitor was used to downregulate the expression of PKC in cardiomyocytes, we found that the role of HSF1 in upregulating ALDH2 beta-MHC weakened. These findings suggest that HSF1 can upregulate the expression of ALDH2 via PKC to promote pressure-stimulated myocardial compensatory hypertrophy, which is an important molecular pathway for HSF1 to ameliorate heart failure.

scholarly journals The Cell Surface Receptors Ror1/2 Control Cardiac Myofibroblast Differentiation

2021 ◽  
Author(s):  
Nicholas W. Chavkin ◽  
Soichi Sano ◽  
Ying Wang ◽  
Kosei Oshima ◽  
Hayato Ogawa ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Fibrosis ◽  
Cardiac Injury ◽  
Pressure Overload ◽  
Orphan Receptor ◽  
Myofibroblast Differentiation ◽  
Transverse Aortic Constriction ◽  
Aortic Constriction ◽  
Cultured Fibroblasts

Background A hallmark of heart failure is cardiac fibrosis, which results from the injury‐induced differentiation response of resident fibroblasts to myofibroblasts that deposit extracellular matrix. During myofibroblast differentiation, fibroblasts progress through polarization stages of early proinflammation, intermediate proliferation, and late maturation, but the regulators of this progression are poorly understood. Planar cell polarity receptors, receptor tyrosine kinase–like orphan receptor 1 and 2 (Ror1/2), can function to promote cell differentiation and transformation. In this study, we investigated the role of the Ror1/2 in a model of heart failure with emphasis on myofibroblast differentiation. Methods and Results The role of Ror1/2 during cardiac myofibroblast differentiation was studied in cell culture models of primary murine cardiac fibroblast activation and in knockout mouse models that underwent transverse aortic constriction surgery to induce cardiac injury by pressure overload. Expression of Ror1 and Ror2 were robustly and exclusively induced in fibroblasts in hearts after transverse aortic constriction surgery, and both were rapidly upregulated after early activation of primary murine cardiac fibroblasts in culture. Cultured fibroblasts isolated from Ror1/2 knockout mice displayed a proinflammatory phenotype indicative of impaired myofibroblast differentiation. Although the combined ablation of Ror1/2 in mice did not result in a detectable baseline phenotype, transverse aortic constriction surgery led to the death of all mice by day 6 that was associated with myocardial hyperinflammation and vascular leakage. Conclusions Together, these results show that Ror1/2 are essential for the progression of myofibroblast differentiation and for the adaptive remodeling of the heart in response to pressure overload.

scholarly journals Caspase-1 Abrogates the Salutary Effects of Hypertrophic Preconditioning in Pressure Overload Hearts via IL-1β and IL-18

2021 ◽  
Vol 8 ◽  
Author(s):  
Fangjie Dai ◽  
Xuan Li ◽  
Xia Li ◽  
Zhiwen Ding ◽  
Ran Xu ◽  
...  
Keyword(s):  
Myocardial Hypertrophy ◽  
Pressure Overload ◽  
Protective Effects ◽  
Transverse Aortic Constriction ◽  
Transient Pressure ◽  
Aortic Constriction ◽  
Caspase 1 ◽  
Unique Model ◽  
Shed Light

Cardiac hypertrophic preconditioning (HP) signifies cardioprotection induced by transient pressure overload to resist hypertrophic effects of subsequently sustained pressure overload. Although it is recently found that inflammation triggers the development of nonischemic cardiomyopathy, whether inflammation plays a role in the antecedent protective effects of HP remains unknown. Caspase-1 is a critical proinflammatory caspase that also induces pyroptosis; thus, we investigated the role of caspase-1 using a unique model of HP in mice subjected longitudinally to 3 days of transverse aortic constriction (TAC 3d), 4 days of de-constriction (De-TAC 4d), and 4 weeks of Re-TAC (Re-TAC 4W). Echocardiography, hemodynamics, histology, PCR, and western blot confirmed preserved cardiac function, alleviated myocardial hypertrophy and fibrosis, and less activated hypertrophic signaling effectors in Re-TAC 4W mice, compared with TAC 4W mice. Mechanistically, caspase-1 and its downstream targets IL-1β and IL-18, but not GSDMD, were less activated in Re-TAC 4W mice. Furthermore, in HP mice with AAV-9-mediated cardiac-specific caspase-1 overexpression, the salutary effects of HP were remarkably abrogated, as evidenced by exacerbated cardiac remodeling, dysfunction, and activation of IL-1β and IL-18. Collectively, this study revealed a previously unrecognized involvement of caspase-1 in cardiac HP by regulation of IL-1β and IL-18 and shed light on caspase-1 as an antecedent indicator and target for cardiac hypertrophy.

Abstract 563: Cardiac TIGAR Reduces Myocardial Energetics and Cardiac Functionin the Pressure Overload Heart Failure Model

2019 ◽  
Vol 125 (Suppl_1) ◽  
Author(s):  
Yoshifumi Okawa ◽  
Atsushi Hoshino ◽  
Tomoya Kitani ◽  
Ryoetsu Yamanaka ◽  
Daichi Hato ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pressure Overload ◽  
Failure Model ◽  
Myocardial Energetics ◽  
Heart Failure Model

scholarly journals A Juvenile Murine Heart Failure Model of Pressure Overload

2010 ◽  
Vol 32 (2) ◽  
pp. 145-153 ◽  
Author(s):  
Kristopher M. Cumbermack ◽  
Jun Cheng ◽  
Yibing Nong ◽  
William T. Mahle ◽  
Ronald W. Joyner ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pressure Overload ◽  
Failure Model ◽  
Heart Failure Model
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