Atherosclerosis
1. Pathogenesis
1) Initiation Fig 241-1
① lipoprotein accumulation & modification
i) fatty streak formation
ii) lipoprotein oxidiation
iii) nonenzymatic glycation: DM환자에서 atherosclerosis를 촉진시키는 기전
② leukocyte recruitment
i) adhesion molecules(VCAM-1, ICAM-1, P-selectin)
ii) cytokines : monocyte & lymphocyte에 의해 IL-1, TNF-α분비
=> VCAM-1, ICAM-1 expression유도
2) Atheroma
① 억제인자
NO, HDL(="reverse cholesterol transport")
thrombomodulin, tissue and urokinase-type plasminogen activator,
heparin sulfate proteoglycan, prostacyclin
② 위험인자
DM, Lp(a), fibrinogen, PAI-1, homocysteine, tobacco, Kawasaki disease
viral & microbial pathogen: Herpesviridiae(CMV포함), Chlamydia
2) atheroma evolution
i) PDGF : smooth muscle cell migration↑
ii) TGF-β: interstitial collagen production↑
iii) serotonin: low molecular weight mediator, smooth muscle fx을 변화시킴
3) clinical syndromes Fig 241-2
atheroma형성 초기에 plaque가 밖으로 자라므로(abluminal direction) 직경은 커진다.
이 현상을 "compensatory enlargment"라 하며 angiography시행시 atherosclerosis를
underestimation하게 된다.
2. 예방 및 치료
1) Risk factors Tab 242-1
homocysteine, Lp(a), infection은 controversial하다(nontraditional risk factor)
① lipid disorder Tab 242-2 NCEP ATP II
HMG CoA reductase inhibitor는 cerebrovascular event에 대하여 LDL lowering benefit을
보이는데 6-24개월의 치료가 필요하다.
② hypertension
thiazide diuretics, β-blocker는 lipid profile에 나쁜 영향을 끼치므로 CHD risk factor or
atherosclerosis가 있을때는 "lipid-neutral" antihypertensive agent(ACE inhibitor &
α-blocker)가 좋다.
③ DM & insulin resistance
insulin resistance와 관련한 abnormal lipoprotein profile을 "diabetic dyslipidemia"라 한다.
HDL↓, TG↑
* ADA recommendation: target LDL = 100 mg/dL↓
④ male gender/postmenopausal state
폐경전 여성은 HDL↑, 폐경후엔 HDL↓ : coronary risk↑
폐경후 ERT: LDL↓, HDL↑
⑤ dysregulated coagulation or fibrinolysis
PAI-1, Lp(a)
⑥ homocysteine
⑦ infection/inflammation : Chlamydia pneumoniae, CMV
⑧ life-style modification
금연, wt reduction, 운동할것