Huoxue Qianyang decoction ameliorates cardiac remodeling in obese spontaneously hypertensive rats in association with ATF6-CHOP endoplasmic reticulum stress signaling pathway regulation

Objective: Endoplasmic reticulum (ER) stress is involved in hypertension related cardiac remodeling. We aimed to evaluate the effects of Huoxue Qianyang (HXQY) decoction on cardiac remodeling in obese spontaneously hypertensive rats (SHRs), and explore its impacts on the activating transcription factor 6 (ATF6)-C/EBP homologous protein (CHOP) ER stress signaling pathway. Methods: Twenty-seven obese SHRs were randomly divided into Obese SHR, Obese SHR + HXQY and Obese SHR + Valsartan groups, and treated with the indicated drugs for 8 weeks. Nine age-matched male SHRs were used as controls. Systolic blood pressure (SBP), body weight (BW), and the left ventricular mass index (LVMI) were measured weekly or at end point. Then, angiotensin II (Ang II), fasting glucose (FPG) and fasting insulin (FIN), total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C) and triglyceride (TG) levels were evaluated with commercial kits. Apoptotic cardiomyocytes were detected by the terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method. The expression levels of GRP78, ATF6, PERK/pPERK and CHOP were assessed by quantitative PCR and Western blot. Results: Treatment with HXQY decoction resulted in significantly reduced SBP, BW, LVMI, Ang II, TC and LDL-C levels, as well as the homeostasis model assessment of insulin resistance (HOMA-IR) score in obese SHRs. Apoptosis in heart tissues of obese SHRs was significantly attenuated after HXQY decoction administration, paralleling reduced expression of GRP78, ATF6, PERK/pPERK and CHOP at both mRNA and protein levels. Conclusion: Cardiac remodeling in obese SHRs is ameliorated by intervention with HXQY decoction in association with inhibited ATF6-CHOP ER stress signaling pathway.