Pathophysiology of Cardiovascular Diseases: New Insights into Molecular Mechanisms of Atherosclerosis, Arterial Hypertension, and Coronary Artery Disease

Abstract

Cardiovascular diseases (CVDs) are disorders associated with the heart and circulatory system. Atherosclerosis is its major underlying cause. CVDs are chronic and can remain hidden for a long time. Moreover, CVDs are the leading cause of global morbidity and mortality, thus creating a major public health concern. This review summarizes the available information on the pathophysiological implications of CVDs, focusing on coronary artery disease along with atherosclerosis as its major cause and arterial hypertension. We discuss the endothelium dysfunction, inflammatory factors, and oxidation associated with atherosclerosis. Mechanisms such as dysfunction of the endothelium and inflammation, which have been identified as critical pathways for development of coronary artery disease, have become easier to diagnose in recent years. Relatively recently, evidence has been found indicating that interactions of the molecular and cellular elements such as matrix metalloproteinases, elements of the immune system, and oxidative stress are involved in the pathophysiology of arterial hypertension. Many studies have revealed several important inflammatory and genetic risk factors associated with CVDs. However, further investigation is crucial to improve our knowledge of CVDs progression and, more importantly, accelerate basic research to improve our understanding of the mechanism of pathophysiology.

Keywords: arterial hypertension; atherosclerosis; cardiovascular disease; coronary artery disease; genetic factor; inflammation; matrix metalloproteinases; oxidative stress; vascular endothelium dysfunction.

Figure 1

Lp-PLA2-dependent activation cycle [40]. The macrophages, lymphocytes, and foam cells present in the atherosclerotic plaques have an influence on the increased level of Lp-PLA2, which in turn catalyzes a reaction that, in the presence of oxidized phospholipids on LDL, is a direct contribution to the secretion of an increased amount of inflammatory mediators, which in turn leads to endothelial dysfunction and further CAD.

Figure 2

The role of SVEP1 in atherosclerosis and CAD [56]. CXCL1 expression is dependent on the presence of SVEP1. Only in the presence of SVEP1 is the CXCL1 expression silenced. Two factors have a significant influence on the expression of CXCL1: MMPs and ADAMTS- 7 (specific metalloproteinases), which can reduce the wildtype SVEP1; mutant SVEP1 (SVEP1_p.D2702G missense variant). Consequently, the secretion and recruitment of inflammatory cells are increased.

Figure 3

Summary of physiological and pathological functions of MMPs. MMPs, matrix metalloproteinases.

Figure 4

MMP-2 cleavage of AM. Adrenomedullin (AM 11–52) is a peptide that affects vessels and leads to its vasodilation. MMP-2 regulates BP by reducing the AM (1–52, 8–52, and 11–52) into smaller peptides AM (11–22), which act as vasoconstrictors. Therefore, MMP-2 may worsen vascular function and increase BP in hypertensive patients. Numbers in brackets are the peptide length before and after the MMP2 cleavage. MMP-2, matrix metalloproteinase 2; AM, adrenomedullin; BP, blood pressure.