Different quantitative apoptotic traits in coronary atherosclerotic plaques from patients with stable angina pectoris and acute coronary syndromes.

Abstract:

BACKGROUND:Apoptosis in human atherosclerotic coronary plaques possibly causes plaque destabilization by contributing to the weakening and breaking down of the fibrous cap. We tested the hypothesis that apoptosis is quantitatively increased in unstable atherosclerotic plaques. METHODS AND RESULTS:We analyzed the expression of apoptotic genes such as BAX, CASP1, FAS, FAS L, FOS, MDM2, NFkB2, P53, PCNA, TERT, and XRCC1 in coronary plaques collected with directional coronary atherectomy from 15 patients with stable angina and 15 with acute coronary syndromes without ST elevation (ACS). Total RNA was extracted and cDNA was amplified with a specific set of primers and TaqMan probes. Apoptosis was also revealed by DNA laddering. To clarify the source of mRNAs, we performed in situ reverse transcriptase-polymerase chain reaction coupled with immunocytochemistry and found a substantial overlap between the mRNAs of the above genes and vascular smooth muscle cells. Gene expression analysis showed that the proapoptotic genes (ie, BAX, CASP1, FAS, FAS L, FOS, NFkB2, P53, PCNA) were significantly more expressed (P<0.001) in ACS plaques, whereas the antiapoptotic genes (ie, MDM2, TERT, XRCC1) were more transcribed (P<0.001) in stable angina plaques. Total gDNA gel electrophoresis identified a laddering pattern in the ACS plaques as evidence of end-point apoptosis. Western blotting substantially confirmed the above data. CONCLUSIONS:Our findings support the idea that ACS plaques are committed to apoptosis through an established meshwork of gene activation and inactivation, whereas stable angina plaques retain active cell homeostasis and repair mechanisms.

journal_name

Circulation

journal_title

Circulation

authors

Rossi ML,Marziliano N,Merlini PA,Bramucci E,Canosi U,Belli G,Parenti DZ,Mannucci PM,Ardissino D

doi

10.1161/01.CIR.0000142865.04816.89

subject

Has Abstract

pub_date

2004-09-28 00:00:00

pages

1767-73

issue

13

eissn

0009-7322

issn

1524-4539

pii

01.CIR.0000142865.04816.89

journal_volume

110

pub_type

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