Citri reticulatae Pericarpium attenuates Ang II-induced pathological cardiac hypertrophy via upregulating peroxisome proliferator-activated receptors gamma

Gehui Ni; Kai Wang; Yufei Zhou; Xiaodong Wu; Jiaqi Wang; Hongcai Shang; Lijun Wang; Xinli Li

doi:10.21037/atm-20-2118

Citri reticulatae Pericarpium attenuates Ang II-induced pathological cardiac hypertrophy via upregulating peroxisome proliferator-activated receptors gamma

Ann Transl Med. 2020 Sep;8(17):1064. doi: 10.21037/atm-20-2118.

Authors

Gehui Ni¹, Kai Wang¹, Yufei Zhou¹, Xiaodong Wu¹, Jiaqi Wang², Hongcai Shang³, Lijun Wang², Xinli Li¹

Affiliations

¹ Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
² Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai, China.
³ Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.

Abstract

Background: Pathological cardiac hypertrophy is a major risk factor for cardiovascular diseases, including heart failure. However, limited pharmacological therapies are available for reversing the maladaptive process and restoring cardiac function. Citri reticulatae Pericarpium (CRP) has been used in traditional Chinese medicine prescriptions for clinical treatment. Previous studies have shown that CRP and its ingredients have beneficial effects on the cardiovascular system. However, whether CRP has a protective effect against pathological cardiac hypertrophy remains unknown.

Methods: Primary neonatal rat cardiomyocytes (NRCMs) were treated with angiotensin II (Ang II) to induce pathological hypertrophy in vitro. Immunofluorescent staining and quantitative real-time PCR (qRT-PCR) were used to determine the cell size and the expression of hypertrophic gene markers (Anp and Bnp), respectively. Male C57BL/6 mice were subjected to the investigation of cardiac hypertrophy induced by Ang II (2.5 mg/kg/d for 4 weeks). CRP (0.5 g/kg/d for 4 weeks) was administrated to treat mice with or without peroxisome proliferator-activated receptors gamma (PPARγ) inhibitor T0070907 (1 mg/kg/d for 4 weeks treatment) infused with Ang II. Cardiac hypertrophy (hematoxylin-eosin staining and qRT-PCR), fibrosis (Masson's Trichrome staining, qRT-PCR, and western blot), and cardiac function (echocardiography) were examined in these mice. Western blot was used to determine the protein level of PPARγ and PGC-1α both in NRCMs and in mice.

Results: We found that CRP could prevent Ang II-induced pathological cardiac hypertrophy evidenced by improving cardiac function, decreasing hypertrophic growth and reducing cardiac fibrosis. Also, we demonstrated that PPARγ was upregulated by CRP both in NRCMs and in hearts. Moreover, PPARγ inhibitor could abolish the inhibitory effects of CRP on Ang II-induced pathological cardiac hypertrophy.

Conclusions: CRP attenuates Ang II-induced pathological cardiac hypertrophy by activating PPARγ.

Keywords: Citri reticulatae Pericarpium (CRP); Pathological cardiac hypertrophy; peroxisome proliferator-activated receptors gamma (PPARγ).