过氧化物酶体增殖物激活受体与炎症:牢记于心。

Peroxisome proliferator-activated receptors and inflammation: take it to heart.

作者信息

Smeets P J H, Planavila A, van der Vusse G J, van Bilsen M

机构信息

Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.

出版信息

Acta Physiol (Oxf). 2007 Nov;191(3):171-88. doi: 10.1111/j.1748-1716.2007.01752.x.

Abstract

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors acting as key regulators of lipid metabolism as well as modulators of inflammation. The role of PPARalpha and PPARgamma in cardiac ischaemia-reperfusion injury, infarct healing and hypertrophy is the subject of intense research. Due to the later development of PPARdelta-specific ligands, the role of this PPAR isoform in cardiac disease remains to be established. Although many studies point to salutatory effects of PPAR ligands in cardiac disease, the exact molecular mechanism is still largely unsolved. Both the metabolic (via transactivation) and the more recently discovered anti-inflammatory (via transrepression) effects of PPARs are likely to play a role. In this review the reported, and sometimes contradictory, effects of PPAR ligands on ischaemia-reperfusion, infarct healing and cardiac hypertrophy are critically evaluated. In particular the role of inflammation in these disease processes, the ability of PPARs to interfere with pro-inflammatory processes, and the mechanisms of transrepression are discussed. Currently, the significance of PPARs as therapeutic targets in cardiovascular disease is receiving widespread attention. Accordingly, detailed understanding of the mechanisms controlling the activity of these nuclear hormone receptors is essential.

摘要

过氧化物酶体增殖物激活受体(PPARs)是配体激活的转录因子,作为脂质代谢的关键调节因子以及炎症调节剂。PPARα和PPARγ在心脏缺血再灌注损伤、梗死愈合和肥大中的作用是深入研究的主题。由于PPARδ特异性配体的研发较晚,该PPAR亚型在心脏疾病中的作用仍有待确定。尽管许多研究表明PPAR配体在心脏疾病中具有有益作用,但其确切的分子机制仍 largely未解决。PPARs的代谢(通过反式激活)和最近发现的抗炎(通过反式抑制)作用可能都发挥了作用。在本综述中,对PPAR配体在缺血再灌注、梗死愈合和心脏肥大方面已报道的、有时相互矛盾的作用进行了批判性评估。特别讨论了炎症在这些疾病过程中的作用、PPARs干扰促炎过程的能力以及反式抑制的机制。目前,PPARs作为心血管疾病治疗靶点的意义正受到广泛关注。因此,详细了解控制这些核激素受体活性的机制至关重要。

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