Theofilis Panagiotis, Sagris Marios, Oikonomou Evangelos, Antonopoulos Alexios S, Lazaros George, Theofilis Anastasios, Papastamos Charalambos, Papaioannou Spyridon, Siasos Gerasimos, Tsioufis Kostas, Tousoulis Dimitris
1st Cardiology Department, Hippokration General Hospital, University of Athens Medical School, Athens, Greece.
3rd Cardiology Department, Sotiria Chest Disease Hospital, University of Athens Medical School, Athens, Greece.
Curr Top Med Chem. 2022;22(28):2355-2367. doi: 10.2174/1568026623666221024091758.
Atherosclerosis and one of its most serious consequences, coronary artery disease, are important sources of morbidity and mortality globally, necessitating early detection and treatment. Considering their complex pathophysiology, including several harmful processes, a comprehensive approach to diagnosis, prognosis, and therapy is very desirable. Extracellular matrix remodeling is a major component of this dangerous cascade, including the cleavage of constituents (collagen, elastin, proteoglycans) and the propagation or exacerbation of the inflammatory response. Several extracellular matrix degradation indicators have been hypothesized to correlate with the existence, severity, and prognosis of coronary artery disease. The potency of matrix metalloproteinases, notably collagenases and gelatinases, has been the most thoroughly investigated in clinical studies. Stromelysins, matrilysins, transmembrane matrix metalloproteinases, collagen and laminin turnover indicators, as well as fibronectin, have also been studied to a lesser level. Among the most well-studied markers, MMP-1, MMP-2, MMP-8, and MMP-9 have been found increased in patients with cardiovascular risk factors such as metabolic syndrome, its components (obesity, dyslipidemia, diabetes mellitus), and smoking. Increasing concentrations are detected in acute coronary syndromes compared to stable angina pectoris and healthy control groups. It should also be stressed that those extracellular matrix biomarkers may also be detected in high concentrations in other vascular pathologies such as peripheral artery disease, carotid artery disease, aortic aneurysms, and dissections. Despite the advances gained, future research should focus on their importance and, more crucially, their added utility as biomarkers in identifying persons at risk of developing overt coronary artery disease. At the same time, determining the prognosis of coronary artery disease patients using such biomarkers may be important for their adequate care.
动脉粥样硬化及其最严重的后果之一——冠状动脉疾病,是全球发病和死亡的重要原因,因此需要早期检测和治疗。鉴于其复杂的病理生理学,包括多种有害过程,采用全面的诊断、预后和治疗方法非常必要。细胞外基质重塑是这一危险级联反应的主要组成部分,包括成分(胶原蛋白、弹性蛋白、蛋白聚糖)的裂解以及炎症反应的传播或加剧。有几种细胞外基质降解指标被认为与冠状动脉疾病的存在、严重程度和预后相关。在临床研究中,基质金属蛋白酶的活性,尤其是胶原酶和明胶酶的活性,得到了最深入的研究。基质溶解素、基质溶素、跨膜基质金属蛋白酶、胶原蛋白和层粘连蛋白周转指标以及纤连蛋白也有较少程度的研究。在研究最多的标志物中,已发现患有心血管危险因素(如代谢综合征及其组成部分(肥胖、血脂异常、糖尿病)和吸烟)的患者体内MMP-1、MMP-2、MMP-8和MMP-9升高。与稳定型心绞痛和健康对照组相比,急性冠状动脉综合征患者体内这些标志物的浓度更高。还应强调的是,在其他血管病变(如外周动脉疾病、颈动脉疾病、主动脉瘤和主动脉夹层)中也可能检测到高浓度的这些细胞外基质生物标志物。尽管已取得进展,但未来的研究应关注它们的重要性,更关键的是,关注它们作为生物标志物在识别有发生显性冠状动脉疾病风险人群方面的额外效用。同时,使用这些生物标志物确定冠状动脉疾病患者的预后可能对其适当治疗很重要。