Jiale He

Abstract

Cocaine abuse has been associated with numerous cardiovascular consequences, such as depressed myocardial contractility, elevated blood pressure, coronary artery vasoconstriction, and myocardial ischemia and infarction. The multifactorial effects of cocaine often contribute to its sympathomimetic function. However, the direct cytotoxic effects of cocaine on the cardiovascular system, especially vascular endothelium, and the cellular and molecular mechanisms remain unknown. The present study was designed to examine the general hypothesis that cocaine induces apoptosis of coronary artery endothelium by suppressing nitric oxide synthesis, stimulating cytochrome c release from mitochondria and subsequently activation of the caspases cascade, which lead to endothelial cell apoptosis. We found that cocaine induces apoptosis of endothelial cells in a dose- and time-dependent manner. The induction of apoptosis by coaine is through the activation of mitochondria-mediated apoptotic pathway. Cocaine-induced mitochondrial cytochrome c release is via bax translocation and decrease of bel-2 level. The decrease of NO production in endothelial cells exposed to cocaine may amplify the apoptotic signals. The studies not only provide a mechanistic basis of endothelium damage in response to cocaine but also enhance our basic understanding of endothelial apoptosis in general and improve our understanding of coronary ischemia, coronary atherosclerosis, and myocardial ischemia and infarction from a new prospective.

LLU Discipline

Pharmacology

Department

Pharmacology

School

Graduate School

First Advisor

Lubo Zhang

Second Advisor

John N. Buchholz

Third Advisor

Carlos A. Casiano

Fourth Advisor

Charles A. Ducsay

Fifth Advisor

Raymond D. Gilbert

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

2001

Date (Title Page)

6-2001

Language

English

Library of Congress/MESH Subject Headings

Cocaine -- pharmacology; Endothelium, Vascular -- cytology; Vastrictor Agentsocons -- pharmacology; Apoptosis -- drug effects -- physiology; Coronary Vessels -- cytology -- drug effects -- metabolism.

Type

Dissertation

Page Count

xiii; 198

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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