Department of Pharmaceutical Sciences, University of Milan, 20133 Milan, Italy.
Laboratory of Neuropharmacology and Epigenetics, Department of Pharmacology, Maj Institute of Pharmacology Polish Academy of Sciences, 31343 Krakow, Poland.
Int J Mol Sci. 2021 Nov 15;22(22):12326. doi: 10.3390/ijms222212326.
Nearly 18 million people died from cardiovascular diseases in 2019, of these 85% were due to heart attack and stroke. The available therapies although efficacious, have narrow therapeutic window and long list of contraindications. Therefore, there is still an urgent need to find novel molecular targets that could protect the brain and heart against ischemia without evoking major side effects. Nuclear receptors are one of the promising targets for anti-ischemic drugs. Modulation of estrogen receptors (ERs) and peroxisome proliferator-activated receptors (PPARs) by their ligands is known to exert neuro-, and cardioprotective effects through anti-apoptotic, anti-inflammatory or anti-oxidant action. Recently, it has been shown that the expression of aryl hydrocarbon receptor (AhR) is strongly increased after brain or heart ischemia and evokes an activation of apoptosis or inflammation in injury site. We hypothesize that activation of ERs and PPARs and inhibition of AhR signaling pathways could be a promising strategy to protect the heart and the brain against ischemia. In this Review, we will discuss currently available knowledge on the mechanisms of action of ERs, PPARs and AhR in experimental models of stroke and myocardial infarction and future perspectives to use them as novel targets in cardiovascular diseases.
2019 年，全球有近 1800 万人死于心血管疾病，其中 85%是由于心脏病发作和中风。现有的治疗方法虽然有效，但治疗窗口狭窄，禁忌症多。因此，仍然迫切需要寻找新的分子靶点，以在不引起重大副作用的情况下保护大脑和心脏免受缺血的影响。核受体是抗缺血药物的一个有前途的靶点。其配体对雌激素受体 (ERs) 和过氧化物酶体增殖物激活受体 (PPARs) 的调节已被证明通过抗细胞凋亡、抗炎或抗氧化作用发挥神经和心脏保护作用。最近，研究表明，脑或心脏缺血后芳烃受体 (AhR) 的表达明显增加，并在损伤部位引发细胞凋亡或炎症的激活。我们假设激活 ERs、PPARs 和抑制 AhR 信号通路可能是保护心脏和大脑免受缺血的一种有前途的策略。在这篇综述中，我们将讨论 ERs、PPARs 和 AhR 在中风和心肌梗死实验模型中的作用机制的现有知识，以及将它们用作心血管疾病新靶点的未来前景。
