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Atherosclerosis

1. Pathogenesis

1) Initiation Fig 241-1

¨ç lipoprotein accumulation & modification

i) fatty streak formation

ii) lipoprotein oxidiation

iii) nonenzymatic glycation: DMȯÀÚ¿¡¼­ atherosclerosis¸¦ ÃËÁø½ÃŰ´Â ±âÀü

¨è leukocyte recruitment

i) adhesion molecules(VCAM-1, ICAM-1, P-selectin)

ii) cytokines : monocyte & lymphocyte¿¡ ÀÇÇØ IL-1, TNF-¥áºÐºñ

=> VCAM-1, ICAM-1 expressionÀ¯µµ

2) Atheroma

¨ç ¾ïÁ¦ÀÎÀÚ

NO, HDL(="reverse cholesterol transport")

thrombomodulin, tissue and urokinase-type plasminogen activator,

heparin sulfate proteoglycan, prostacyclin

¨è À§ÇèÀÎÀÚ

DM, Lp(a), fibrinogen, PAI-1, homocysteine, tobacco, Kawasaki disease

viral & microbial pathogen: Herpesviridiae(CMVÆ÷ÇÔ), Chlamydia

2) atheroma evolution

i) PDGF : smooth muscle cell migration¡è

ii) TGF-¥â: interstitial collagen production¡è

iii) serotonin: low molecular weight mediator, smooth muscle fxÀ» º¯È­½ÃÅ´

3) clinical syndromes Fig 241-2

atheromaÇü¼º Ãʱ⿡ plaque°¡ ¹ÛÀ¸·Î ÀÚ¶ó¹Ç·Î(abluminal direction) Á÷°æÀº Ä¿Áø´Ù.

ÀÌ Çö»óÀ» "compensatory enlargment"¶ó Çϸç angiography½ÃÇà½Ã atherosclerosis¸¦

underestimationÇÏ°Ô µÈ´Ù.

2. ¿¹¹æ ¹× Ä¡·á

1) Risk factors Tab 242-1

homocysteine, Lp(a), infectionÀº controversialÇÏ´Ù(nontraditional risk factor)

¨ç lipid disorder Tab 242-2 NCEP ATP II

HMG CoA reductase inhibitor´Â cerebrovascular event¿¡ ´ëÇÏ¿© LDL lowering benefitÀ»

º¸À̴µ¥ 6-24°³¿ùÀÇ Ä¡·á°¡ ÇÊ¿äÇÏ´Ù.

¨è hypertension

thiazide diuretics, ¥â-blocker´Â lipid profile¿¡ ³ª»Û ¿µÇâÀ» ³¢Ä¡¹Ç·Î CHD risk factor or

atherosclerosis°¡ ÀÖÀ»¶§´Â "lipid-neutral" antihypertensive agent(ACE inhibitor &

¥á-blocker)°¡ ÁÁ´Ù.

¨é DM & insulin resistance

insulin resistance¿Í °ü·ÃÇÑ abnormal lipoprotein profileÀ» "diabetic dyslipidemia"¶ó ÇÑ´Ù.

HDL¡é, TG¡è

* ADA recommendation: target LDL = 100 mg/dL¡é

¨ê male gender/postmenopausal state

Æó°æÀü ¿©¼ºÀº HDL¡è, Æó°æÈÄ¿£ HDL¡é : coronary risk¡è

Æó°æÈÄ ERT: LDL¡é, HDL¡è

¨ë dysregulated coagulation or fibrinolysis

PAI-1, Lp(a)

¨ì homocysteine

¨í infection/inflammation : Chlamydia pneumoniae, CMV

¨î life-style modification

±Ý¿¬, wt reduction, ¿îµ¿ÇÒ°Í