HIF-1α knockdown attenuates phenotypic transformation and oxidative stress induced by high salt in human aortic vascular smooth muscle cells

Increased dietary salt intake is a well-established risk factor for hypertension and related cardiovascular diseases, involving complex vascular remodeling processes. However, the specific role of hypoxia-inducible factor-1 alpha (HIF-1 alpha) in vascular pathophysiology under high-salt conditions remains poorly understood. This study investigates the role of HIF-1 alpha in high-salt-induced vascular remodeling using human aortic vascular smooth muscle cells (HA-VSMCs) cultured in vitro. HA-VSMCs were divided into three groups: high-salt with HIF-1 alpha knockdown (shHIF-1 alpha + HS), negative control (shcontrol), and high-salt (HS). Cell viability, migration, gene expression, and protein levels were evaluated. High-salt conditions significantly increased mRNA expression of alpha-smooth muscle actin (alpha-SMA), smooth muscle protein 22 (SM22), angiotensin II type 1 receptor (AT1R), collagen I, and collagen III (p < 0.0001). HIF-1 alpha knockdown partially attenuated these increases, particularly for alpha-SMA, SM22, and AT1R (p < 0.01). At the protein level, high-salt exposure markedly elevated expression of collagen III, HIF-1 alpha, osteopontin (OPN), and angiotensin II (Ang II) (p < 0.0001). HIF-1 alpha knockdown significantly reduced the high-salt-induced increases in collagen III and HIF-1 alpha protein levels (p < 0.001) but had a limited effect on OPN and Ang II upregulation. Interestingly, SM22 protein expression was significantly decreased under high-salt conditions (p < 0.0001), an effect partially reversed by HIF-1 alpha knockdown (p < 0.0001). These findings demonstrate that high-salt conditions induce complex changes in gene and protein expression in HA-VSMCs, with HIF-1 alpha playing a crucial role in mediating many of these alterations. The study highlights the differential effects of HIF-1 alpha on various markers of vascular remodeling and suggests that HIF-1 alpha may be a potential therapeutic target for mitigating salt-induced vascular pathology. Further research is warranted to elucidate the mechanisms underlying the HIF-1 alpha-dependent and -independent effects observed in this study.