Kao Ting-Wei, Huang Chin-Chou
Department of Internal Medicine, National Taiwan University Hospital, Taipei 100225, Taiwan.
Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112201, Taiwan.
Int J Mol Sci. 2022 Jan 12;23(2):804. doi: 10.3390/ijms23020804.
Phenotyping cardiovascular illness and recognising heterogeneities within are pivotal in the contemporary era. Besides traditional risk factors, accumulated evidence suggested that a high inflammatory burden has emerged as a key characteristic modulating both the pathogenesis and progression of cardiovascular diseases, inclusive of atherosclerosis and myocardial infarction. To mechanistically elucidate the correlation, signalling pathways downstream to Toll-like receptors, nucleotide oligomerisation domain-like receptors, interleukins, tumour necrosis factor, and corresponding cytokines were raised as central mechanisms exerting the effect of inflammation. Other remarkable adjuvant factors include oxidative stress and secondary ferroptosis. These molecular discoveries have propelled pharmaceutical advancements. Statin was suggested to confer cardiovascular benefits not only by lowering cholesterol levels but also by attenuating inflammation. Colchicine was repurposed as an immunomodulator co-administered with coronary intervention. Novel interleukin-1β and -6 antagonists exhibited promising cardiac benefits in the recent trials as well. Moreover, manipulation of gut microbiota and associated metabolites was addressed to antagonise inflammation-related cardiovascular pathophysiology. The gut-cardio-renal axis was therein established to explain the mutual interrelationship. As for future perspectives, artificial intelligence in conjunction with machine learning could better elucidate the sequencing of the microbiome and data mining. Comprehensively understanding the interplay between the gut microbiome and its cardiovascular impact will help identify future therapeutic targets, affording holistic care for patients with cardiovascular diseases.
在当代，对心血管疾病进行表型分析并识别其中的异质性至关重要。除了传统风险因素外，越来越多的证据表明，高炎症负担已成为调节心血管疾病（包括动脉粥样硬化和心肌梗死）发病机制和进展的关键特征。为了从机制上阐明这种相关性，Toll样受体、核苷酸寡聚化结构域样受体、白细胞介素、肿瘤坏死因子及相应细胞因子下游的信号通路被认为是发挥炎症作用的核心机制。其他显著的辅助因素包括氧化应激和继发性铁死亡。这些分子层面的发现推动了药物研发的进展。他汀类药物不仅被认为可通过降低胆固醇水平，还可通过减轻炎症来赋予心血管益处。秋水仙碱被重新用作与冠状动脉介入治疗联合使用的免疫调节剂。新型白细胞介素-1β和-6拮抗剂在最近的试验中也显示出有前景的心脏益处。此外，对肠道微生物群及其相关代谢产物的调控被用于对抗与炎症相关的心血管病理生理学。由此建立了肠-心-肾轴来解释它们之间的相互关系。至于未来展望，人工智能与机器学习相结合可以更好地阐明微生物组的序列和数据挖掘。全面了解肠道微生物群与其心血管影响之间的相互作用将有助于确定未来的治疗靶点，为心血管疾病患者提供全面的护理。
