The burden of cold-induced hypertension: Integrating molecular mechanisms and preventive strategies

Hypertension constitutes one of the most prominent risk factors for cardiovascular and cerebrovascular diseases, chronic renal disease, and dementia. The risk of hypertension and mortality is greater in winter than in summer, with cold exposure serving as a significant factor in the cardiovascular disease (CVD) burden under suboptimal temperatures. Exposure to cold conditions facilitates the development of hypertension and is strongly associated with subsequent cardiovascular incidents. This review meticulously consolidates recent developments in the comprehension of cold-induced hypertension (CIH). Mechanistically, CIH is primarily regulated by the neuroendocrine axis, which is mediated by the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS); it also encompasses molecular mechanisms such as the oxidative stress-inflammation cascade, regulation of gut microbiota regulation, adipose tissue metabolism, and ion channel function. By incorporating public health strategies and synthesizing current research on the prevention and treatment of CIH, we examine the future potential of personalized prevention through natural products and RNA, with the goal of offering guidance for forthcoming regional public health policies and research initiatives. Molecular mechanisms of cold-induced hypertension. Abbreviations: AngⅡ, angiopoietin-2; ANP, atrial natriuretic peptide; AR, adrenoceptor; BAT, brown adipose tissue; BNP, brain natriuretic peptide; CK, creatine kinase; EF, ejection fraction; EPHX2, epoxide hydrolase 2; ET-1, endothelin-1; ET-A, endothelin A; ET-B, endothelin B; FAO, fatty acid oxidation; FFA, fundus fluorescein angiography; IL-1β, interleukin-1 beta; IL-6, Interleukin-6; LDH, lactate dehydrogenase; MYH7, myosin heavy chain 7; NO, nitric oxide; NOX, nitric oxide receptor; SNF, sympathetic nerve fibers; SOD2, superoxide dismutase 2; SNS-RAAS, sympathetic nervous system-renin-angiotensin-aldosterone system; TNF α, tumor necrosis factor; UCP1, uncoupling Protein 1. • Links cold exposure to hypertension based on clinical evidence. • Cold exposure elevates BP and may program hypertension in offspring. • Provides the first comprehensive review of CIH pathogenesis and prevention strategies.