Peroxisome proliferator-activated receptors as biomarkers in cerebrovascular diseases: A narrative review

Xiangyi Xu a, Qianqian Chen a, Shun Li b, Tianqing Xiong a b c 1

a Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China

b Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

c Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Yangzhou University, Yangzhou, Jiangsu Province, China

Received 23 December 2024, Accepted 7 January 2025, Available online 10 January 2025, Version of Record 10 January 2025.

https://doi.org/10.1016/j.neumar.2024.100035

Abstract

Cerebrovascular disease, a critical global health challenge, profoundly affects the quality and longevity of human life due to its alarmingly high incidence, disability, mortality, recurrence rate, and extensive complications. The underlying risk factors, particularly the combined effects of hypertension, hyperlipidemia, and hyperglycemia, exacerbate this disease burden. Recent breakthroughs have highlighted the role of biomarkers, specifically peroxisome proliferator-activated receptors, as a member of the nuclear transcription factor family, in regulating essential physiological and pathological processes, including fat metabolism, inflammation, cancer progression, neurodegeneration, and cardiovascular health. This paper reviews the role of peroxisome proliferator-activated receptors (PPARs) in cerebrovascular disease and its associated risk factors. It focuses on the three core members of the PPAR family—PPARα, PPARβ/δ, and PPARγ—which play a crucial role in regulating the complex network of cerebrovascular diseases and their associated risk factors. These three PPAR isoforms not only regulate the balance and distribution of lipids in the body by finely tuning various aspects of fat metabolism, but also modulate key physiological and pathological processes, including inflammatory responses, cell proliferation, and differentiation. The mechanisms by which PPARs operate are both complex and subtle, and their widespread influence makes them potential bridges between basic research and clinical practice. Developing targeted interventions for PPARs to enable precision medicine and personalized management of cerebrovascular diseases could provide more effective, safer, and tailored treatment options for patients with these conditions.

作为脑血管疾病生物标志物的过氧化物酶体增殖物激活受体：叙述性综述

摘要

脑血管疾病是全球健康领域的一项严峻挑战，以其惊人的高发病率、高致残率、高死亡率、高复发率以及伴随而来的广泛并发症，对人类的生活质量和寿命产生着深远的影响。其潜在的危险因素，尤其是高血压、高脂血症和高血糖的交织效应，加剧了这一疾病负担。近年来，突破性研究发现，核转录因子超家族成员之一的过氧化物酶体增殖激活受体（PPARs）在调节脂肪代谢、炎症、癌症进展、神经变性和心血管健康等多个关键生理和病理过程中发挥着不可或缺的作用。文章回顾了过氧化物酶体增殖激活受体（PPARs）在脑血管疾病和风险因素中的作用，特别强调了再生医学领域（如血管再生）的最新进展，并讨论了 PPARs 家族的3个核心成员： PPAR α，PPAR β/δ 和 PPAR γ 在脑血管疾病及其相关风险因素的复杂网络中编织了一张精密的调控网。这3种表型不仅通过精确调控脂肪代谢的每一个微小环节来影响脂质在体内的平衡和分布，还深入干预炎症反应的启动和抑制、细胞增殖和分化等关键生理和病理过程，为脑血管疾病的预防和治疗开辟了新的思路和途径。它们的作用机制既复杂又微妙，既广泛又深入，正逐渐成为连接基础研究与临床实践的桥梁。展望未来，进一步探索 PPARs 的分子机制，揭示其在脑血管疾病和危险因素中的特异性作用途径和调控网络，将是推动再生医学发展的重要方向。在此基础上，开发针对PPARs靶点的特异性干预手段，实现脑血管疾病管理的精准化和个体化，有望为广大患者带来更加有效、安全和个性化的治疗方案，从而减轻这一全球性疾病的沉重负担，提高人类整体健康水平。