Hyperhomocysteinemia-induced Nrf2/HO-1 pathway suppression aggravates cardiac remodeling of hypertensive rats

Abjective: Interaction of hypertension and hyperhomocysteinemia (HHcy) leads to enhanced cardiac remodeling in hypertensive heart disease. However, the mechanism of collagen accumulation and cardiac remodeling remains unclear. In this study, we attempted to evaluate the relationship between hypertension and HHcy in the context of cardiac remodeling and to explore its mechanism of action. Methods: Wistar Kyoto (WKY) and spontaneous hypertension rats (SHR) were randomly divided into four groups, namely WKY group, WKY + HHcy group, SHR group and SHR + HHcy group. We measured blood pressure (BP), plasma homocysteine (Hcy), serum superoxide dismutase (SOD) and serum malondialdehyde (MDA). We also examined cardiac histopathology and gene and protein expression levels of Nrf2 and HO-1. Results: Compared with the WKY group, myocardial interstitial and perivascular collagen deposition in the WKY + HHcy group, the SHR group and the SHR + HHcy group increased successively, indicating that cardiac remodeling gradually increased, and HHcy aggravated cardiac remodeling was more serious in hypertensive rats. SOD decreased gradually in the four groups, while MDA was on the contrary. WKY + HHcy and SHR + HHcy groups both suppressed Nrf2 and HO-1 expression and inhibited the translocation of Nrf2 from cytoplasm to nucleus compared with their control groups, and the SHR + HHcy group had a stronger inhibitory effect. Conclusion: HHcy enhanced cardiac remodeling in rats by enhancing oxidative stress, suppressing the Nrf2/HO-1 pathway and Nrf2 nuclear transport, and this inhibitory effect was stronger in the context of hypertension. (c) 2021 Elsevier Inc. All rights reserved.

Automated summary

The interaction of hypertension and HHcy can lead to enhanced cardiac remodeling, especially in hypertensive rats. HHcy promotes cardiac remodeling by enhancing oxidative stress, suppressing the Nrf2/HO-1 pathway, and inhibiting Nrf2 nuclear transport, with a stronger inhibitory effect in the presence of hypertension.