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PPAR 调节在心血管疾病血管生成中的药理学作用。

Pharmacological Utility of PPAR Modulation for Angiogenesis in Cardiovascular Disease.

机构信息

CNRS, INSERM, Université Côte d'Azur, iBV, 06107 Nice, France.

出版信息

Int J Mol Sci. 2023 Jan 25;24(3):2345. doi: 10.3390/ijms24032345.


DOI:10.3390/ijms24032345
PMID:36768666
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9916802/
Abstract

Peroxisome proliferator activated receptors, including PPARα, PPARβ/δ, and PPARγ, are ligand-activated transcription factors belonging to the nuclear receptor superfamily. They play important roles in glucose and lipid metabolism and are also supposed to reduce inflammation and atherosclerosis. All PPARs are involved in angiogenesis, a process critically involved in cardiovascular pathology. Synthetic specific agonists exist for all PPARs. PPARα agonists (fibrates) are used to treat dyslipidemia by decreasing triglyceride and increasing high-density lipoprotein (HDL) levels. PPARγ agonists (thiazolidinediones) are used to treat Type 2 diabetes mellitus by improving insulin sensitivity. PPARα/γ (dual) agonists are supposed to treat both pathological conditions at once. In contrast, PPARβ/δ agonists are not in clinical use. Although activators of PPARs were initially considered to have favorable effects on the risk factors for cardiovascular disease, their cardiovascular safety is controversial. Here, we discuss the implications of PPARs in vascular biology regarding cardiac pathology and focus on the outcomes of clinical studies evaluating their benefits in cardiovascular diseases.

摘要

过氧化物酶体增殖物激活受体,包括 PPARα、PPARβ/δ 和 PPARγ,是配体激活的转录因子,属于核受体超家族。它们在葡萄糖和脂质代谢中发挥重要作用,也被认为可以减轻炎症和动脉粥样硬化。所有的 PPAR 都参与血管生成,这一过程对心血管病理学至关重要。所有的 PPAR 都有合成的特异性激动剂。PPARα 激动剂(贝特类)通过降低甘油三酯和增加高密度脂蛋白(HDL)水平来治疗血脂异常。PPARγ 激动剂(噻唑烷二酮类)通过提高胰岛素敏感性来治疗 2 型糖尿病。PPARα/γ(双重)激动剂被认为可以同时治疗这两种病理状况。相比之下,PPARβ/δ 激动剂尚未在临床应用。尽管最初认为激活 PPAR 对心血管疾病的危险因素有有利影响,但它们的心血管安全性仍存在争议。在这里,我们讨论了 PPAR 在心脏病理学方面的血管生物学意义,并重点关注了评估其在心血管疾病中益处的临床研究结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d9/9916802/55c631a03ec4/ijms-24-02345-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d9/9916802/55c631a03ec4/ijms-24-02345-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d9/9916802/55c631a03ec4/ijms-24-02345-g001.jpg

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Pharmacological Utility of PPAR Modulation for Angiogenesis in Cardiovascular Disease.

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本文引用的文献

[1]
Effect of Statins on All-Cause Mortality in Adults: A Systematic Review and Meta-Analysis of Propensity Score-Matched Studies.

J Clin Med. 2022-9-25

[2]
Angiotensin II receptor type 1 blocker candesartan improves morphine tolerance by reducing morphine‑induced inflammatory response and cellular activation of BV2 cells via the PPARγ/AMPK signaling pathway.

Mol Med Rep. 2022-10

[3]
Telmisartan is the most effective ARB to increase adiponectin via PPARα in adipocytes.

J Mol Endocrinol. 2022-5-10

[4]
NSAIDs and Cancer Resolution: New Paradigms beyond Cyclooxygenase.

Int J Mol Sci. 2022-1-27

[5]
PPAR control of metabolism and cardiovascular functions.

Nat Rev Cardiol. 2021-12

[6]
Aspirin for Primary Prevention of Cardiovascular Disease in the 21 Century: A Review of the Evidence.

Am J Cardiol. 2021-4-1

[7]
High-resolution 3D imaging uncovers organ-specific vascular control of tissue aging.

Sci Adv. 2021-2-3

[8]
PPARs and Myocardial Infarction.

Int J Mol Sci. 2020-12-11

[9]
Decreased blood vessel density and endothelial cell subset dynamics during ageing of the endocrine system.

EMBO J. 2021-1-4

[10]
PPARs and Angiogenesis-Implications in Pathology.

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