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Adaptive-Outward and Maladaptive-Inward Arterial Remodeling Measured by Intravascular Ultrasound in Hyperhomocysteinemia and Diabetes

Santhosh K. G. Koshy, MD, DM

Sanjeev Wasson, MD

Division of Cardiology, University of Missouri Hospital, Columbia, MO

Edwin E. Quan, MD

Sebastian Pagni, MD

Department of Cardiothoracic Surgery, University of Louisville School of Medicine, Louisville, KY

Andrew M. Roberts, PhD

Irving G. Joshua, PhD

Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, KY

Suresh C. Tyagi, MPhi, PhD

Department of Physiology and Biophysics, University of Louisville School of Medicine, A-1115, 500 South Preston Street, Louisville, KY 40202; s0tyag01{at}louisville.edu

Background: Coronary artery remodeling implies structural changes in the vessel wall in response to various pathophysiologic conditions. However, the classification of remodeling is unclear. We hypothesized that the adaptive, positive-outward remodeling is a reactive and compensatory response to the stress. The maladaptive negative-inward constrictive remodeling is a passive atherosclerotic condition in which the vessel becomes stiffer.

Methods: Patients with atherosclerotic lesions underwent intravascular ultrasound (IVUS) scans. The size of the vessels distal to and proximal to plaques were analyzed by IVUS. Diabetes was created in mice by an intraperitoneal injection of alloxan (65 mg/kg). To reduce remodeling, mice received ciglitazone, an agonist of peroxisome proliferators activated receptor-g (PPARg) in drinking water. After 8 weeks, atherosclerotic vessels were analyzed for collagen and elastin.

Results: IVUS data suggest an adaptive coronary arterial remodeling was a positive compensatory response to various pathologic stimuli; for example, with the deposition of atherosclerotic plaque, coronary arterial segments enlarged to maintain luminal area. This phenomenon was commonly observed during the initial phases of the development of atherosclerosis. However, negative coronary artery remodeling, or a decrease in vessel area with the formation of atherosclerotic plaque, was maladaptive and was associated with smoking, hypertension, hyperhomocysteinemia, diabetes mellitus, and also after percutaneous coronary interventions (restenosis). In diabetic mice, there was increased collagen and decreased elastin contents; however, treatment with ciglitazone ameliorated the decrease in elastin contents.

Conclusion: Global enlargement of the coronary vascular tree occurs during pressure and volume overload associated with ventricular hypertrophic states such as athletic conditioning, hypertensive heart disease, and dilated cardiomyopathy. On the other hand, maladaptive coronary arterial remodeling occurs in patients with severe deconditioning, diabetes mellitus, after coronary artery bypass surgery, and in some instances, postintervention.

Key Words: plaque rupture • fibrous cap • atherosclerosis • collagen • elastin • matrix metalloproteinase • tissue inhibitor of matrix metalloproteinase • endothelial • macrophage

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