Fibrous cap

Acute coronary syndromes most often result from a physical disruption of the fibrous cap, either frank cap fracture or superficial endothelial erosion, allowing the blood to make contact with the thrombogenic material in the lipid core or the subendothelial region of the intima. This contact initiates the formation of a thrombus, which can lead to a sudden and dramatic blockade of blood flow through the affected artery. If the thrombus is nonocclusive or transient, it may either be clinically silent or manifest as symptoms characteristic of unstable angina. Importantly, if collateral vessels have previously formed, for example, due to chronic ischemia produced by multi vessel disease, even total occlusion of one coronary artery may not lead to an acute myocardial infarction. 

Lipid-laden macrophages, smooth muscle cells, and necrotic debris from the death of foam cells accumulate in the subendothelial space, leading to enlargement of the fatty streak. A collagen matrix forms a fibrous cap that covers the lipid core of the lesion to establish a fibrous plaque called an atherosclerotic plaque. Initially, the diameter of the coronary artery lumen is... 

In Apo E-deficient animals fed a normal chow diet, fatty streaks are first observed in the proximal aorta at 10 to 12 weeks (15). The xanthoma that forms in the intima contains foam cells and is often called the early atherosclerotic lesion and is critically dependent on monocytes. Smooth muscle cells (SMCs) arrive in the intima at approximately 15 weeks and form a fibrous cap around 20 weeks (16). By 36 weeks, lumen narrowing occurs in the external branches of the carotid artery (incidence -75%), but the lumen size is maintained in the aorta. Lumen narrowing, or stenosis, does not correlate with plaque size but... 

Fig. 11.1. Atherogenesis is a persistent inflammatory response that occurs in response to conditions that cause endothelial damage (e.g., hypercholesterolemia and oxLDL). After endothelial cells are activated, they elaborate cytokines, chemokines, and other mediators that recruit mononuclear cells (monocytes and T lymphocytes) to extravasate into the vessel wall where they are activated and release additional proinflammatory factors. Macrophages are able to take up oxLDL via scavenger receptors causing them to differentiate into foam cells and form a fatty streak that progresses to an atheroma with a necrotic lipid core and a fibrous cap. Chemokines can lead to weakening of the fibrous cap and eventual plaque rupture leading to thrombosis and occlusion of the involved vessel.

The cause of ACS in more than 90% of patients is rapture, Assuring, or erosion of an unstable atheromatous plaque. Plaques most susceptible to rupture have an eccentric shape, thin fibrous cap, large fatty core, high content of inflammatory cells such as macrophages and lymphocytes, limited amounts of smooth muscle, and significant compensatory enlargement. 

Repeated injury and repair within an atherosclerotic plaque eventually lead to a fibrous cap protecting the underlying core of lipids, collagen, calcium, and inflammatory cells such as T lymphocytes. Maintenance of the fibrous plaque is critical to prevent plaque rupture and subsequent coronary thrombosis. 

As the fatty streak enlarges over time, necrotic tissue and fiee lipid accumulates, surrounded by epithelioid cells and eventually smooth muscle cells, an advanced plaque with a fibrous cap. The plaque eventually begins to occlude the blood vessel, causing ischemia and infarction in the heart, brain, or extremities. 

Eventually the fibrous cap may thin, and the plaque becomes unstable, leading to rupture and thrombosis. 

The interactions of these cells with T lymphocytes also in the lesion and the overlying endothelium can lead to a massive flbroproliferative response over which connective tissue from smooth muscle cells form a fibrous cap. This covers the advanced lesion or fibrous plaque of atherosclerosis, deeper portions of which consist of macrophages, T lymphocytes, smooth muscle cells, connective tissue, necrotic debris and varying amounts of lipids and lipoproteins. 

At autopsy, a ruptured plaque features a thin fibrous cap overlying cell-rich regions with a lipid-rich necrotic core (<3 mm ) containing cell debris. The indicators for plaque instability include an inflammatory infiltrate with lipid-rich macrophages (foam-cells) and a decreased collagen and smooth muscle cell (SMC) content in the fibrous caps as well as at the shoulders of the atheroma, respectively. Therefore, one of the challenges of modern medicine is the design of... 

Thin fibrous cap + lipid core + dense macrophages... 

In the upper panel, a vulnerable plaque is demonstrated with thin fibrous cap, large lipidcore, and increased density of microphages. In the lower panel, a plaque rupture with accompanying thrombi is shown. 

The CRP levels were determined in these patients. It was higher in patients with plaque rupture (21 patients) compared with those without plaque rupture (24 patients)—3.1 0.5 mg/L versus 1.9 0.4mg/L (P = 0.04). This suggests that an elevated CRP reflects an inflammatory process that can lead to plaque rupture. The CRP seems to have independent predictive capacity for identifying inflammation here. There is also a possibility that CRP may release factors that further weaken the plaque s fibrous cap and allow rupture or erosion (16). 

Furthermore, Ang n has been found to contribute to VSMC senescence, which has been implicated in the pathogenesis of atherosclerosis (Kunieda et al. 2006). Cell senescence may promote plaque instability, since loss of VSMCs leads to transformation into a rupture-prone plaque with a thin fibrous cap over the lipid-rich core (Geng and Libby 2002). 

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