Progression, Regression, and Remodeling of Atherosclerosis ( 동맥경화증의 진행, 퇴축, 그리고 재성형 ) Hyo-Soo Kim, MD, PhD Cardiovascular Center, Seoul National University Hospital, Seoul, Korea 김 효 수 서울대학교병원 심혈관센터 서울대학교 의과대학 내과학교실

The Spectrum of Vascular Remodeling Gibbons G & Dzau VJ NEJM 1994;330;1431-8

Clinical Conditions involving Vascular Remodeling Gibbons G & Dzau VJ NEJM 1994;330;1431-8

Longitudinal & Cross Sectional Images (Positive Remodeling) Schoenhagen P,, Nissen SE, Tuzcu EM. JACC 2001;38;

Extremes of Vascular Remodeling RR = EEM area lesion / EEM area prox reference Schoenhagen P,, Nissen SE, Tuzcu EM. JACC 2001;38;

Tomographic Sections of Human Coronary Artery (IVUS image) Schoenhagen P,, Nissen SE, Tuzcu EM. JACC 2001;38;

Tomographic Sections of Human Coronary Artery (IVUS image) Birnbaum Y,, Siegel RJ. JACC 1997;30;

Negative Remodeling (RR = 11.5/16.0 = 0.71) Positive Remodeling (RR = 18.9/14.9 = 1.32)

Various Types of Vascular Remodeling Schoenhagen P,, Nissen SE, Tuzcu EM. JACC 2001;38;

Nissen SE & Yock P. Circulation 2001;103; Positive Remodeling at Early Stage of Atherosclerosis Results in False Negative on CAG Distal Reference Positive Remodeling at Early Lesion

Nissen SE & Yock P. Circulation 2001;103; Negative Remodeling in addition to Neointimal Formation Results in Significant Stenosis on CAG Distal Reference Stenotic Lesion

The Possible Sequential Changes of Atherosclerotic Artery ( based on the postmortem analysis of 136 LMCA ) Glagov S, et al. NEJM 1987;316; Early Phase : Overcompensation Vss Enlargement > Plaque Accumulation Late Phase : Decompensation Vss Enlargement < Plaque Accumulation

Segmental Comparison between Normal and Atherosclerotic Human Coronary Artery Zarins CK,, Glagov S. J Vasc Surg 1988;7;386. Pts = 125 LAD = 481 segs LAD with Atherosclerosis : Plaq Area correlates with Vss Area : compensatory enlargement : esp, at distal segment LAD in best quartile LAD in worst quartile

Birnbaum Y,, Siegel RJ. JACC 1997;30; Two Extremes of Vascular Remodeling

Nishioka T,, Siegel RJ. JACC 1996;27; (+) (-) Proportions of Positive or Negative Remodeling (IVUS Data of Human Coronary Primary Atherosclerosis)

Nishioka T,, Siegel RJ. JACC 1996;27; # Mintz GS, et al. Circulation 1997;95;1791 Lim TT, et al. Circulation 1997;95; Proportions of Positive or Negative Remodeling (IVUS Data of Human Coronary Primary Atherosclerosis) 55%20% 25% 15% or 22% in other studies#

Siegel RJ, et al. [letter] Circulation 1996;94; Saphenous Vein Graft Atherosclerosis at the Site of Venous Valves

Nishioka T,, Siegel RJ. Circulation 1996;93; Absence of Positive Remodeling in Saphenous Vein Bypass Graft ( IVUS Data )

Schoenhagen P,, Nissen SE, Tuzcu EM. JACC 2001;38; Direction of Remodeling & Plaque Stability

Nissen SE & Yock P. Circulation 2001;103; Direction of Remodeling & Plaque Stability Early Phase of Atherosclerosis Compensatory Enlargement Positive Remodeling Unstable Plaque Late Phase of Atherosclerosis Shrinkage of Vessel Negative Remodeling Stable Plaque

Nissen SE & Yock P. Circulation 2001;103; Ruptured Plaque with Positive Remodeling Prox Reference Ruptured Plaque

Summary of Vascular Remodeling in Native Coronary Atherosclerosis 1. Sequential Change of Remodeling (in Histologic study) Compensatory enlargement at early phase No lumen loss until plaque area reaches 40% of EEM area 2. Proportion of Remodeling (in IVUS study) 50% of lesions show compensatory enlargement 15 ~ 25 % of lesions show vascular shrinkage Shrinkage is highly associated with lesion calcification 3. Special Issues on Compensatory Enlargement impaired in DM & smokers & saphenous vein graft greater in eccentric lesion or concentric lesion ?

Mechanism of Positive Remodeling in Early Atherosclerosis Medial change Atherosclerosis  Atrophy & thinning of media  weakening of the arterial wall  dilatation Shear stress change Expanding atheroma  lumen narrowing  increased shear stress  dilatation with normalization of shear stress

Mechanism of Negative Remodeling Early event ? (failure of the adaptive compensatory dilation) Calcified lesion is highly associated with negative remodeling Fibrocalcific element limits adaptive positive remodeling ? Late event ? (active arterial shrinkage) Mature plaque with increased fibrous and calcific deposits & apoptosis as well as decreased lipid content results in retraction Contributing factor ? (Venturi effect) Vascular narrowing  rapid flow & low pressure  shrinkage

Serial Observation of Arterial Remodeling Schoenhagen P,, Nissen SE, Tuzcu EM. JACC 2001;38;

Luo H,, Siegel RJ. ATVB 1996;16; Association of Remodeling & Restenosis after Coronary Balloon Angioplasty Restenotic Patent

Summary of Vascular Remodeling during Restenosis after PTCA or DCA 1.Vascular shrinkage is important determinant for restenosis 75% of luminal loss d/t decrease of EEM area 25% of luminal loss d/t increase of Plaque area 2. Shrinkage is more important for restenosis after balloon or DCA with shallow injury 3. Intimal hyperplasia is more important for restenosis after DCA with deep injury or stenting DM pts

Mechanism of Negative Remodeling after PTCA or DCA Adventitial role Overstretch & deep tear  Inflammation & proliferation & differentiation of Fb to myofibroblast  Contraction of adventitial scar  Late lumen narrowing Determinant of Remodeling Direction ? Severity and depth of the wall injury Extent of inflammatory reaction Pressure, wall stress, & flow through lesion

The Agents of Vascular Remodeling Gibbons G & Dzau VJ NEJM 1994;330;1431-8

The Factors that modulate the Growth of VSMC Gibbons G & Dzau VJ NEJM 1994;330;1431-8

Mediators of Vascular Remodeling in ECM Gibbons G & Dzau VJ NEJM 1994;330;1431-8

Progression, Regression, and Remodeling Glagov S, et al. NEJM 1987;316;

Atherosclerosis Regression Trial with IVUS F/U by Lipid-Lowering Agent REVERSAL (Reversal of Atherosclerosis with Lipitor) Nissen SE. AJC 2000;86(suppl 1);12-17H.