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