动脉型肺动脉高压与冠状动脉疾病和肾脏疾病的分子机制关联

Molecular Mechanisms of Pulmonary Arterial Hypertension and Coronary Artery Disease and Kidney Disease

摘要

动脉型肺动脉高压(PAH)是一种以肺小血管持续性收缩、进行性闭塞和重塑为特征的严重肺循环疾病,最终可导致右心衰竭甚至死亡。近年来研究表明,PAH并非仅局限于肺部,而是与全身多个系统病变密切相关,但其具体的关联机制尚未完全阐明。本文发现,PAH与冠状动脉疾病(CAD)及肾脏疾病(KD)可能共享某些分子异常表达机制。例如,BRD4、NF-κB、HMGB1和NFAT的异常表达共同参与PAH与CAD的发病;而JAG1、LTB4及NRF2的失调则与PAH和KD均相关。这些相似的分子机制提示,PAH与CAD、KD等疾病在发生发展过程中可能存在内在联系,这可以为深入理解多种疾病的发病机制及研发PAH的精准化治疗提供新的思路。

Abstract

Pulmonary arterial hypertension (PAH) is a severe pulmonary circulatory disorder characterized by progressive occlusion and remodeling of small pulmonary vessels, ultimately leading to right heart failure and even death. Recent studies suggest that PAH is not confined to the lungs but is closely associated with systemic multi-organ pathologies. However, the precise mechanisms underlying these associations remain incompletely elucidated. This review reveals that PAH may share certain aberrant molecular expression mechanisms with coronary artery disease (CAD) and kidney disease (KD). The dysregulated expression of BRD4, NF-κB, HMGB1, and NFAT contributes to both PAH and CAD, while dysfunctions of the JAG1, LTB4, and NRF2 are implicated in both PAH and KD. These overlapping molecular mechanisms suggest an intrinsic link between PAH, CAD, and KD in their initiation and progression and may thus provide new insights into the pathogenesis of multiple diseases and the development of targeted therapeutic strategies for PAH.

关键词

动脉型肺动脉高压 / 冠状动脉疾病 / 肾脏疾病 / 分子机制

Key words

pulmonary arterial hypertension (PAH) / coronary artery disease (CAD) / kidney diseases (KD) / molecular mechanism

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基金资助

国家科技重大专项(2024ZD0528600)

国家自然科学基金项目(82241014)

国家自然科学基金项目(82130002)