The complex puzzle underlying the pathophysiology of acute coronary syndromes: from molecular basis to clinical manifestations

Abstract

Acute coronary syndromes (ACS) still represent a major cause of death in Western countries; in the vast majority of cases, coronary atherosclerosis represents the common pathological lesion to all forms of ACS. It is currently believed that plaque complication (rupture, fissuration, and so on), with the consequent superimposed thrombosis, is a key factor ultimately leading to the clinical occurrence of ACS. Over the last two decades, our understanding of the basic mechanisms involved in the pathophysiology of ACS has progressed significantly and the crucial role of inflammation in this phenomenon is now widely recognized. The sequence of events is represented by plaque complication (i.e., rupture, fissuration or erosion), exposure of tissue factor and other prothrombotic substances, such as von Willebrand factor and collagen, to the blood flow, activation of platelets and of the coagulation cascade and thrombus formation within the coronary artery. However, not all complicated plaques cause the clinical occurrence of ACS and similar complicated plaques may cause different clinical manifestations. A complex interaction between different factors, such as arterial vessel wall substrates, degree of inflammation of the culprit lesion, local rheological characteristics of blood flow, as well as factors present in the circulating blood, will determine the severity (complete vs incomplete occlusion) and the persistence of coronary blood flow cessation, which, in turn, will be largely responsible for the clinical picture. Targeting tissue factor, the key player in the activation of the coagulation cascade, may represent an important therapeutic strategy to prevent the clinical manifestation of ACS.

Elevated Plasma Level of Pentraxin-3 Predicts In-Hospital and 30-Day Clinical Outcomes in Patients with Non-ST-Segment Elevation Myocardial Infarction Who Have Undergone Percutaneous Coronary Intervention

“…The most common cause of ACS is the rupture of a ‘vulnerable' atherosclerotic coronary plaque. Other coronary events, such as coronary embolism, coronary vasospasm, drug ingestion or spontaneous coronary artery dissection, also contribute to a reduction in coronary blood flow, causing myocardial ischemia [21,22]. If the episode of myocardial ischemia is temporary, cardiac symptoms are present transiently and serologic evidence of myonecrosis is absent, leading to a diagnosis of unstable angina.…”

Reactive oxygen species induce a procoagulant state in endothelial cells by inhibiting tissue factor pathway inhibitor

“…Coronary thrombosis generally occurs at sites of a preexisting atherosclerotic plaque often precipitated by fissuration or ulceration of the plaque [1]. Several studies have identified both TF antigen and activity within human atherosclerotic plaques and have suggested that they might represent an important determinant of thrombogenicity Fig.…”

“…Specifically, we have investigated how ROS affect a cell population never investigated before in this context and that is known to be a primary source of TFPI such as HCAECs [18]. This is an important pathophysiological issue since at the endothelial cell surface, a dynamic interaction exits between mechanisms inhibiting and promoting activation of coagulation [1,2]. Unperturbed endothelial cells physiologically produces several chemical mediators, including TFPI, able to inhibit intravascular thrombus formation [29][30][31].…”

“…Binding of TF to its natural ligand, factor VII (FVII), induces factor Xa (FXa) and thrombin generation, finally leading to intravascular thrombus formation. To avoid improper thrombus formation, three major regulatory routes strictly control the coagulation process [1]. First, direct enzyme inhibitors are present to regulate free coagulation enzymes, limiting the coagulation response to the site of injury.…”

Identification of gene variants related to the nitric oxide pathway in patients with acute coronary syndrome

“…Acute coronary syndrome (ACS) arises from the formation of thrombus at damaged atherosclerotic plaques in coronary arteries [1][2][3][4][5][6][7][8][9][10][11]. Acute coronary syndrome is a complex disease determined by both genetic and environmental issues.…”