GPCR agonist-induced transactivation of the EGFR upregulates MLC II expression and promotes hypertension in insulin-resistant rats

摘要

Aims The presence of metabolic abnormalities such as insulin resistance and elevated levels of various vasoconstrictor G-protein-coupled receptor (GPCR) agonists contributes to the development of hypertension. Recent studies have suggested a link between disease progression and activation of growth factor receptor signalling pathways such as the epidermal growth factor receptor (EGFR) by matrix metalloproteinases (MMPs). We hypothesized that excessive stimulation of GPCRs such as α₁-adrenergic receptors activates MMP-dependent EGFR transactivation and contributes to the development of hypertension by promoting increased synthesis of contractile proteins in vascular smooth muscle (VSM).