HDL elevation and lipid lowering therapy: current scenario and future perspectives.
High density lipoprotein (HDL) has proven its role in reverse cholesterol transport and cellular cholesterol efflux thus acting as a protective factor against atherogenic cardiovascular diseases. The article focuses primarily on structure and function of genes influencing HDL metabolism. Various novel targets involve liver X receptor, retinoid X receptor, peroxisome proliferators activated receptor agonists and apoA-I mimetics. New molecules targeting these nuclear receptors are described. Phospholipid transfer protein and scavenger receptor B1 are also attractive targets in HDL metabolism. ATP-Binding Cassette transporter A1 and several lipases also play a crucial role in HDL metabolism and are very useful target for atherogenic dyslipidemia. Cholesteryl ester transfer protein inhibitors have shown great promise as possible drug candidates of future. Notably, JTT-705 (Japan Tobacco, Roche) is of great interest in spite of withdrawal of torcetrapib. Considering modest effect of currently available therapeutic options on HDL, these novel HDL elevating targets are doubtlessly the target for future atherosclerotic intervention.
Chhabria
Mahesh T
MT
Department of Pharmaceutical Chemistry and Quality Assurance, L M College of Pharmacy, Navrangpura, Ahmedabad - 380 009, Gujarat, India. mahesh.chhabria@rediffmail.com
Suhagia
Bhanubhai N
BN
Brahmkshatriya
Pathik S
PS
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology; D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics / Q000502:physiology; D018955:CD36 Antigens / Q000235:genetics / Q000502:physiology; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors; D008076:Cholesterol, HDL / Q000097:blood* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000819:agonists / Q000235:genetics / Q000502:physiology; D050171:Dyslipidemias / Q000378:metabolism / Q000517:prevention & control*; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008049:Lipase / Q000502:physiology; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000235:genetics / Q000502:physiology; D047488:Retinoid X Receptors / Q000819:agonists / Q000235:genetics / Q000502:physiology
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D018955:CD36 Antigens; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D004268:DNA-Binding Proteins; D000960:Hypolipidemic Agents; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047492:Peroxisome Proliferator-Activated Receptors; D049294:Phospholipid Transfer Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D047488:Retinoid X Receptors; D008049:Lipase