Exaggerated myocardial oxLDL amount and LOX-1 receptor over-expression associated with coronary microvessel inflammation in unstable angina

Abstract The pathophysiological relationship between coronary atherosclerosis and coronary microvessels remains undefined and the specific causative role of oxidatively modified low density lipoprotein (oxLDL) in human atherosclerosis is debated. The purposes of this study are to investigate whether...

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Published in:	Atherosclerosis Vol. 226; no. 2; pp. 476 - 482
Main Authors:	Neri Serneri, Gian Gastone, Coppo, Mirella, Bandinelli, Manuela, Paoletti, Paoletto, Toscano, Thomas, Micalizzi, Ezio, Chiostri, Marco, Boddi, Maria
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier Ireland Ltd 01-02-2013 Elsevier
Subjects:	Adult Aged Angina Pectoris - physiopathology Angina, Unstable - physiopathology Atherosclerosis Atherosclerosis (general aspects, experimental research) Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Cardiovascular Coronary Artery Disease - physiopathology Coronary heart disease Coronary microvessels Coronary Vessels - pathology Female Heart Humans Inflammation Inflammation - pathology Inflammation - physiopathology Lipoproteins, LDL - blood Male Medical sciences Middle Aged Octamer Transcription Factor-1 - biosynthesis oxLDL RNA, Messenger - metabolism Scavenger Receptors, Class E - biosynthesis STAT1 Transcription Factor - biosynthesis oxLDL Inflammation Coronary microvessels Atherosclerosis Vascular disease Cardiovascular disease Coronary heart disease Variant angina
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Summary:	Abstract The pathophysiological relationship between coronary atherosclerosis and coronary microvessels remains undefined and the specific causative role of oxidatively modified low density lipoprotein (oxLDL) in human atherosclerosis is debated. The purposes of this study are to investigate whether coronary microvessels are involved in coronary atherosclerosis and whether increased myocardial oxLDL amount can be associated with coronary microvessel inflammation. A combination of immunohistochemical, RT-PCR and real-time PCR studies performed on myocardial biopsy specimens from patients with mitral stenosis (control hearts, CHs) and from unstable and stable angina patients (UAP and SAP), demonstrated that myocardial oxLDL was associated with a chronic low-grade inflammation in SAP and with a severe high grade inflammation in UAP. oxLDL amount was notably higher in UAP than in SAP and in UAP the high grade of inflammation was correlated with the increased amount of oxLDL in endothelial cells and macrophages. The exaggerated amount of oxLDL in UAP and the interaction of oxLDL with lectin-like oxLDL (LOX-1) receptor are amplified by the activation of transcriptional factor octamere 1 (OCT-1) with consequent activation of a series of inflammatory endothelial feed-back mechanisms resulting in LOX-1 gene over-expression, endothelial inflammation as well as uncontrolled nuclear factor kappa B (NFkB) activation. Moreover, in UAP genes for signal transducer and activator transcriptional factor 1α (STAT1α), angiotensin converting enzyme (ACE) and numerous pro-inflammatory cytokines were over-expressed. The present results may have clinical relevance because they show that coronary atherosclerosis is a disease not confined to the large arteries but involving the whole coronary tree. In UAP the exaggerated amount of myocardial oxLDL is associated with widespread high grade microvessel inflammation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0021-9150 1879-1484
DOI:	10.1016/j.atherosclerosis.2012.11.007