Atherosclerosis I Flashcards
Arteriosclerosis
“hardening of the arteries”
- affects mainly arterioles
- associated with chronic hypertension (response to HTN)
- narrowing of lumen
Tissue response to endothelial damage/injury:
Inflammation and Healing Response
-intimal thickening as site of accumulation of lipid
deposition and macrophage activation
-hyperplasia of media due chronic inflammation
-smooth muscle cells synthesis of extracellular matrix
molecules that directly influence the hardening (act as
fibroblasts)
-proliferation and migration into intima
two forms of atherosclerosis
-two forms: hyaline arteriolosclerosis, hyperplastic
arteriolosclerosis
Atherosclerosis
-basic lesion is atheroma (fibrofatty plaque)
-disease of large elastic arteries and large and medium
sized muscular arteries
-prime targets: aorta, coronary arteries, cerebral
arteries
characteristics of atherosclerosis
-progressive (inflammatory) disease of the walls of
large and medium sized muscular arteries of
-older adults
-lipid-containing plaques result in narrowing of the
vessel lumen
-chronic inflammatory reaction to deposited
oxidized lipid
-thrombotic/embolic obstruction of blood vessels of
the heart, brain, kidney, and lower extremities
pathogenesis of atherosclerosis
-Inflammatory/healing reaction of the endothelium of large
and medium sized arteries
-focal lesions within the intima (NOT involving media or
adventitia except secondarily)
what are the two main features separate this reaction from normal inflammatory events seen in small blood vessels
- accumulation of cholesterol as a result of insudation and
uptake of oxidized LDL by monocytes/macrophages and
smooth muscle cells - substitution of smooth muscle cells for fibroblasts in the
healing phase which give rise to a fibrous cap and
deposition of ECM components.
cell types involved
- endothelial cells
- monocytes/macrophages
- smooth muscle cells which migrate from the media
- platelets
- lymphocytes
6th major component
consists of serum lipids in the form of LDL or VLDL. These lipoproteins carry cholesterol, triglycerides, and phospholipids to peripheral tissues
evolution of atherosclerosis lesions
-local endothelial injury/accumulation of lipid
-endothelial cell activation
-adhesion of platelets and monocytes
-secretion of inflammatory cytokines
-migration/proliferation of cells activated by
cytokines which then secrete extracellular matrix
components (in this case smooth muscle cells).
lesions progression of age
Earliest lesions are tiny accumulations of lipid
within monocytes which give rise to fatty streaks
-flat, multifocal
With aging, the lesions become raised and
coalesce into plaques
-plaques are raised and show evidence of
extracellular lipid accumulation and
migration/proliferation of smooth muscle cells in the
intima (from the media).
characteristic distribution
- abdominal aorta
- carotid arteries
- coronary arteries
- proximal arteries of the lower extremities
where can atherosclerotic be found
Found at branching points and ostia of vessels
-increased blood flow and turbulence of flow
appear to play a role
consequences of lesions in middle sized vessels
progressive luminal narrowing
-results in progressive compromise of blood flow and
chronic ischemia
-thrombotic events associated with fissuring or rupture of
the atherosclerotic plaque are associated with acute
infarction
consequences of lesions in large vessels
(aorta) weakening of the arterial wall also results in aneurysms
- distortion of the wall architecture
- release of embolic material from disrupted plaques
risk factors
related to key pathogenic features of the development of
atherosclerotic lesions:
-ENDOTHELIAL CELL DAMAGE
-SERUM CHOLESTEROL LEVELS
Damage to the endothelium + insudation of lipid leads to
chronic inflammatory response mediated by macrophages
(cytokines); smooth muscle cells migrate to intima to
produce fibrosis and calcification
major risk factors
- Hypertension
- Smoking - toxic effect on endothelium
- Hyperlipidemia/cholesterol levels
- Diabetes
hypertension as a risk factor
- increased mechanical damage to endothelium
- increased mechanical deposition of lipid
hyperlipidemia as a risk factor
- Increased deposition of oxidized LDL and cholesterol
- Higher LDL and triglycerides increase risk
- Higher HDL decreases risk
diabetes as a risk factor
- ?hyperglycemia toxic to endothelium
- Increased fatty acids and serum lipids
minor risk factors
-age (not usually symptomatic until >age 50)
-sex: males show more progressive lesions at ages
<50; females show relative protection until
menopause; after menopause the sex-based
differences disappear
-obesity, metabolic syndrome
-“stress” – type A personalities, sedentary lifestyle
-lipoprotein (a) – altered form of LDL that contains
apolipoprotein B-100 linked to apoliprotein A
-oral contraceptives - associated with thrombotic events
-hypothyroidism, hyperuricemia, homocysteine levels
infections associations with atherosclerosis
Chlamydia pneumoniae; herpesvirus (HCMV, EBV)
-accelerated atherogenesis of cardiac transplants is
associated with HCMV infection in immunosuppressed
patients
-appropriate antibiotic therapy reduces clinical events in patients with ischemic heart disease
what is another risk factor for atherosclerosis
-elevated C-reactive protein levels (cardiovascular
events)
-acute phase protein associated with inflammatory
response
-associated with increased risk of acute coronary
syndrome
-elevated homocysteinuria - causes ?endothelial
dysfunction, interferes with nitric oxide; also
prothrombotic, increases collagen production
risk factors for atherosclerosis
- genetics: how our body handles lipids
- smoking
- age: happens over decades
- hypertension
- obesity, diabetes type II-> related to hypertension, also type I related to atherosclerosis
