Cold exposure-induced pathophysiological changes and related diseases: recent advances

doi:10.12092/j.issn.1009-2501.2026.07.015

Abstract

Abstract:

Under cold conditions, organism activate the hypothalamic thermoregulatory center, initiating a neuroendocrine-metabolic cascade to maintain core body temperature homeostasis. This process simultaneously induces both adaptive and pathophysiological alterations. Cold exposure triggers key pathophysiological including enhanced thermogenesis, energy metabolism reprogramming, vasomotor dysfunction, immune regulation imbalance, overactivation of renin-angiotensin-aldosterone system (RAAS), and multi-system damage and dysfunction. These alterations are closely associated with the development and progression of frostbite, cardiovascular and cerebrovascular diseases (such as hypertension, atrial fibrillation, myocardial infarction, heart failure, and stroke), and respiratory diseases (including asthma and chronic obstructive pulmonary disease). This article systematically reviews the physiological compensatory mechanisms induced by cold exposure and recent research advances concerning their mediation of common cold-related diseases, thereby providing a theoretical basis for the precision prevention and treatment of cold-associated disorders.

Key words: cold exposure, energy metabolism reprogramming, vascular dysfunction, immune dysregulation, renin-angiotensin-aldosterone system, pathophysiological mechanisms

CLC Number:

R645
R339.6

Shunfang ZUO, Huali XU, Linyu LI, Tianlang LI, Wenwen FU, Yan XUE. Cold exposure-induced pathophysiological changes and related diseases: recent advances[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(7): 990-1000.

Figures/Tables 1

Fig.1 Summary of pathophysiological changes linking cold exposure to related diseases Cold exposure triggers two primary thermogenic responses: shivering thermogenesis (ST) and non-shivering thermogenesis (NST). The activation of adipose tissue facilitates these processes, but an inadequate energy supply can precipitate systemic hypothermia. Concurrently, cold stress activates the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS). The interplay of these systems promotes the development of hypertension and cardiac overload. Furthermore, cold-induced vascular dysfunction contributes to tissue hypoxia, ischemia, and an increased susceptibility to infection. Collectively, these pathways drive the progression of cardiovascular and cerebrovascular diseases, including myocardial infarction and stroke. Simultaneously, immune dysregulation— characterized by inflammation, oxidative stress, and immunosuppression— exacerbates tissue damage and promotes the onset of respiratory diseases and multi-organ injury.

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