PDGF : released by activated platelets(locally adherent), disrupted endothelial cells, and

infiltrating macrophages promotes migration of SMs from media into the intima and increase SMCs
proliferation. Platelets also release TGF-beta which is chemotactic for SMCs and induces interstitial
collagen production.

........
fibroblast are found infrequently in the tunica intima of blood vessels and are not significantly
involved in atherosclerosis pathogenesis.
....
Vascular smooth muscle cells(VSMC) are directly responsible for the synthesis of new collagen
and extracellular matrx

Endothelial Cell Injury is due to hyperlipidemia and chronic hemodynamic stress.>>>>

this leads to increased expression of surface vascular cell-adhesion molecules (VCAM)>>>>that allow
adherence and migraton of monocytes and T lymphocytes into the intima>>>>the infiltrating
leukocytes and dysfunctional endothelium release cytokines and growth factor.( eg
PDGF,FGF,endothelin-1, interleukin-1) that promote migration and proliferation of VSMC from
media within intima.
VSMC are also stimulated to synthesize extracellular matrix proteins (eg collagen,
elastin,proteoglycans) that form the fibrous cap typical of mature atheroma.
COMPLICATONS :the likely hood of plaque rupture or other acute plaque change has more to do
with plaque stability than plaque size.
plaque stability depends upon mechanical strength of overlying fibrous cap.

during chronic inflammatory progression of an atheroma, the fibrous cap is continually being
remodeled. the balance of collagen synthesis and degredation determine the mechanical
strength of the cap.
activated macrophages in the atheroma contribute to collagen degredation by secreting
metalloproteinases.thus a high degree of ongoing intimal inflammation can destabilize the
mechainical integrity of plaque through release of the metallopreoteinases.
.........
macrophage also produce matrix metalloproteinases and tissue factors that degrade the
extracelular matrix,causing the formation of a large, soft lipid-rich core with thinning of the fibrous
cap. such vulnerable plaques have an increased propensity for rupture.
.
ATHEROMAS :start as early as 2nd decade with formation of fatty streak and intimal thickening
..........
fatty streak : presents as minimally raised yellow spots in the inner surface of vessels, these
are the earliest lesions in the progression to atherosclerosis and can be seen as early as the
second decade of life.with advancing age, the chronic inflammatory process initiated by
endothelial injury transitions from fatty streaks within the intima (composed mainly of
lipid-laden foam cells) into atherosclerotic plaques, such as fibrous cap atheromas and
fibrous plaques
...........................................................................................................

subendothelial collagen and subendothelial glycosaminoglycan form subendothelial fibrous

cap over the central core of an atherosclerotic plaque.
........
thin fibrous cap, rich lipid core and active inflammation all correlate with decrease plaque
stability.
.........
more advance lesion develop lipid-rich necrotic core and regions of calcification.
......
Abs to oxidized LDL have been detected in human serum and localize to atherosclerotic
plaque.
titer of this rises following acute coronary event.
although they play a role in atherosclerosis development , they do not act as growth
factors for SMc
.......
total coronary artery calcium content correlate modestly with coronary artery
atherosclerotic plaque burden.
but the presence of intraplque calcium could be consistent with either acute coronary
syndrome or with gradual occlusion without mycardial necrosis.
.

Isolated systemic hypertension is due to decrease in compliance of aorta and its major
branches with progressoin