Importance of blood cellular genomic profile in coronary heart disease.
Since receptor/transcription factor family especially peroxisome proliferator-activated receptors PPARs (alpha, gamma) and liver X receptor alpha (LXRalpha) have been recognized to play crucial role in both lipid metabolism and inflammation, the present study was addressed to explore the interrelationship between blood cellular genomic expression profile, serum lipid levels and severity of coronary heart disease (CHD) in human subjects. Based upon the demographic and laboratory data, the human subjects were divided into 4 groups. Genomic expression profile in the subjects belonging to these groups was determined by measuring the transcriptional expression of genes coding for PPARs (alpha, gamma), CD36, LXRalpha and low density lipoprotein receptor (LDLR) in their blood mononuclear cells. This genomic expression profile was correlated with serum lipid profile as well as with the severity of CHD (revealed by coronary angiography coupled with modified Gensini score) using standard statistical analytical methods. Further in vitro and in vivo effect of statins on such genomic profile was also explored. Although genes coding for PPARs (alpha, gamma), CD36, LDLR showed correlation with the severity of coronary atherosclerosis , blood cellular LXRalpha genomic profile showed conspicuous negative correlation with the severity of coronary atherosclerosis in subjects with or without hypercholesterolemia. This view was further confirmed in experiments directed to understand the effect of statins on the cellular genomic profile of PPARs (alpha, gamma) and LXRalpha. Based on these reported findings, we propose that blood cellular LXRalpha genomic profile has a protective effect against the development of CHD and hence may be of importance in devising synthetic therapeutic drugs for CHD in future.
Baba
M Iqbal
MI
Department of Experimental Medicine & Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India. dkaul_24@hotmail.com
Kaul
Deepak
D
Grover
Anil
A
D000328:Adult; D000368:Aged; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D003327:Coronary Disease / Q000097:blood / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D023281:Genomics; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000502:physiology; D000071518:Liver X Receptors; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D057093:Orphan Nuclear Receptors; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000097:blood; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D013223:Statistics as Topic
D018955:CD36 Antigens; D004268:DNA-Binding Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D047492:Peroxisome Proliferator-Activated Receptors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011973:Receptors, LDL