title: 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.
  
  
  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.
authors.affiliation: Division of Cardiology, Istituto Clinico Humanitas, Milan, Italy. marcolrossi@hotmail.com
authors.forename: Marco L
authors.initials: ML
authors.lastname: Rossi
authors.forename: Nicola
authors.initials: N
authors.lastname: Marziliano
authors.forename: Piera Angelica
authors.initials: PA
authors.lastname: Merlini
authors.forename: Ezio
authors.initials: E
authors.lastname: Bramucci
authors.forename: Umberto
authors.initials: U
authors.lastname: Canosi
authors.forename: Guido
authors.initials: G
authors.lastname: Belli
authors.forename: Dennis Zavalloni
authors.initials: DZ
authors.lastname: Parenti
authors.forename: Pier Mannuccio
authors.initials: PM
authors.lastname: Mannucci
authors.forename: Diego
authors.initials: D
authors.lastname: Ardissino
mesh_terms: D000208:Acute Disease; D000787:Angina Pectoris / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D017209:Apoptosis / Q000235:genetics; D017073:Atherectomy; D020170:Caspase 1 / Q000096:biosynthesis / Q000235:genetics; D003324:Coronary Artery Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004562:Electrocardiography; D053222:Fas Ligand Protein; D020869:Gene Expression Profiling; D016762:Genes, fos; D016158:Genes, p53; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D052003:NF-kappa B p52 Subunit; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D051736:Proto-Oncogene Proteins c-mdm2; D012333:RNA, Messenger / Q000096:biosynthesis; D012422:Rupture, Spontaneous; D019098:Telomerase / Q000096:biosynthesis / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D000076105:X-ray Repair Cross Complementing Protein 1; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics
chemical_list: C494826:BAX protein, human; D004268:DNA-Binding Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D052003:NF-kappa B p52 Subunit; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C509186:TERT protein, human; D019098:Telomerase; D020170:Caspase 1