Coronary artery disease pathophysiology The term coronary artery disease encompasses a range of diseases that result from

atheromatous change in coronary vessels. In the past, CAD was thought to be a simple, inexorable process of artery narrowing, eventually resulting in complete vessel blockage (and Myocardial Infarction). However, in recent years the explanatory paradigm has changed because it was realized that a whole spectrum of coronary plaques exists from stable (lipid-poor, thick fibrous cap) to unstable (lipidrich, thin fibrous cap) (see Figure 1). When an unstable plaque ruptures and the more unstable it is, the more likely it is to rupture the subsequent release of prothrombotic and vasoconstrictive factors increases the likelihood of complete occlusion of the artery. It is the balance between the bodys prothrombotic and thrombolytic pathways at the rupture site that determines the clinical outcome. Transient occlusion leads to ischemia and pain; permanent occlusion leads to transmural MI. Figure 1
An atherosclerotic plaque consists of a core of dead foam cells (lipid-engorged macrophages and smooth muscle cells) covered by a fibrous cap (a region of the intimal layer that has become thickened as a result of medial smooth muscle cells depositing collagen and elastin fibers). The thickening artery wall of an atherosclerotic plaque gradually encroaches upon the luminal space and can eventually result in a restriction to blood flow. Unstable plaques, which are susceptible to rupture, are softer with a thinner fibrous cap. Plaque rupture triggers the formation of a blood clot, which can block the flow of blood through the artery. RBC: red blood cell; WBC: white blood cell. stable unstable ruptured

Abundant smooth muscle cell

Abundant macrophages and lipid rich

Thin fibrous cap

fibrin,white blood cell, red blood cell, platelet, ruptures

Atherosclerosis is initiated by a combination of circulating factors, such as cholesterol, and hemodynamic forces (common sites for atherosclerosis are areas where arteries branch). LDL and

circulating leukocytes penetrate the arterial wall at regions of high shear stress (turbulent flow). In its atherogenic oxidized form, LDL enters macrophages, converting them to foam cells in the process. Oxidized LDL also enhances the growth factor-mediated migration of monocytes and smooth muscle cells to the intima, where the latter differentiate to form the fibrous cap of the mature atherosclerotic plaque. Figure 2 shows the layers of a vessel wall. As a result of our understanding of these processes, there is much experimental interest in factors that contribute to the attraction and adhesion of leukocytes (chemokines and adhesion molecules), the receptors that modulate LDL uptake (scavenger receptors), enzymes that degrade the cap (matrix metalloproteinases), and protective species (such as nitric oxide). With inflammation a central component of our current appreciation of atherosclerosis, there is much interest in circulating markers (such as C-reactive protein) and pharmaceutical interventions that decrease inflammation (aspirin and statins). Figure 2

intima

Internal elastic lamina

Media layer

eksternal elastic lamina

adventitia

Source : Coronary Artery Disease. In: Ashley EA, Niebauer J, editors. Cardiology explained. London: Remedica; 2004. p. 45