מתוך medicontext.co.il
By Karla Gale
WESTPORT, CT (Reuters Health) – A new class of compounds may be more effective than statins in reducing plasma lipid levels, according to data from an animal model of hypercholesterolemia.
The compounds are ligands designed to bind to sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP), French investigators report in Nature Medicine for December.
Dr. Thierry Grand-Perret and associates at GlaxoSmithKline used human hepatoma cells containing the human low density lipoprotein (LDL) receptor promoter. When loaded with sterols, the basal LDL receptor promoter activity declined to less than one third of that observed in control cells. Under these same conditions, the SCAP ligands activated the LDL receptor promotor several-fold.
In fat-fed hamsters treated for 3 days with one of the ligands, very low density lipoprotein cholesterol was reduced by 82%, and LDL and triglycerides by 64%. High density lipoprotein cholesterol level was not significantly affected.
Dr. Grand-Perret and his associates propose that SCAP ligands "trigger the proteolytic maturation of SREBPs and their migration in the nucleus leading to the transcriptional activation of target genes such as LDL receptor." Statins, on the other hand, deplete cellular cholesterol and derepress SCAP, they point out.
In response to these findings, Dr. Daniel J. Rader, of the University of Pennsylvania School of Medicine in Philadelphia, suggests that "the major need for new LDL-lowering drugs is for use in combination with statins."
"Statins are generally very well tolerated and proven effective in reducing cardiovascular risk," he told Reuters Health. "There is no real need for a 'substitute' except for the minority of people who don't tolerate statins."
Dr. Rader points out that SCAP ligands may induce potentially toxic increases in cellular cholesterol and should therefore be carefully evaluated for safety.
He also notes that other new approaches to reduce plasma LDL cholesterol are being evaluated in current trials. These include inhibitors of the intestinal bile acid transporter and of the microsomal triglyceride transfer protein. "These alternative approaches, like SCAP ligands, are likely to work by themselves as well as in combination with statins," he said.
e-Med Tools
קצר קולע וממוקד
e-Med סמינרים
אי-מד תחקירים
Medscape Tools
Journal Club
מרכזי מידע ושירות
Facebook
מידע למפרסם
מאגר תרופות
מאגר אנשי המקצוע
אינדקס שימושי
חדשות משה"ב
eMed HealthClub
מחקרים קליניים
השאירו תגובה
רוצה להצטרף לדיון?תרגישו חופשי לתרום!