New Sides of Aldosterone Action in Cardiovascular System as Potential Targets for Therapeutic Intervention

Kołodziejczyk, Patrycjusz; Gromotowicz-Popławska, Anna; Aleksiejczuk, Michal; Chabielska, Ewa; Tutka, Piotr; Miltyk, Wojciech

doi:10.2174/1389450119666180326125926

Cited by 5 publications

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“…Recent studies have shown that the rapid nongenomic effects of aldosterone are closely related to aldosterone-induced myocardial remodeling [ 7 , 8 ]. Aldosterone binds and activates the cytoplasmic mineralocorticoid receptor (MR), which acts as a nuclear transcription factor to induce the expression of specific mRNAs [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Zi Shen Huo Luo Formula Prevents Aldosterone‐Induced Cardiomyocyte Hypertrophy and Cardiac Fibroblast Proliferation by Regulating the Striatin‐Mediated MR/EGFR/ERK Signaling Pathway

Feng

Zhao

Song

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Inappropriate activation of the renin-angiotensin-aldosterone system (RAAS) is an important factor in the development of hypertension. Excessive aldosterone can lead to myocardial extracellular matrix collagen proliferation, fibrosis, and cardiomyocyte hypertrophy and aggravate maladaptive remodeling. The results of our previous clinical and animal experiments suggested that Zi Shen Huo Luo Formula (ZSHLF) combined with perindopril can effectively control the process of left ventricular hypertrophy (LVH). The purpose of this study was to investigate whether ZSHLF-treated serum inhibits the membrane localization of the striatin-mediated mineralocorticoid receptor (MR) and affects MR-mediated nongenomic effects and the downstream epidermal growth factor receptor (EGFR)/extracellular regulated kinase (ERK) signaling pathways, thereby improving aldosterone-induced myocardial remodeling. Serum containing ZSHLF was prepared and used to treat rat cardiomyocytes and cardiac fibroblasts in vitro after aldosterone induction and striatin knockdown by small interfering RNA (siRNA). Cell-based assays were carried out to determine the cardiomyocyte surface area and assess the proliferation rate and hydroxyproline secretion of cardiac fibroblasts. Quantitative real-time PCR (qRT-PCR), immunoprecipitation (IP), and Western blotting were performed to evaluate the striatin-mediated MR/EGFR/ERK signaling pathway. In the present study, ZSHLF attenuated the aldosterone-induced hypertrophy of cardiomyocytes and inhibited the proliferation and collagen synthesis of cardiac fibroblasts. ZSHLF also reduced striatin mRNA expression and inhibited striatin and MR binding, membrane MR protein expression, and EGFR and ERK1/2 phosphorylation. Furthermore, after striatin silencing with siRNA, some of the effects of ZSHLF were not changed significantly. In conclusion, ZSHLF inhibits the downstream EGFR/ERK signaling pathway by blocking the striatin-mediated membrane localization of MR, which may be an important molecular mechanism by which ZSHLF improves aldosterone-induced myocardial remodeling.

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