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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:2014.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Phospholipid Transfer Protein–Deficient Mice Absorb Less Cholesterol

Ruijie Liu; Jahangir Iqbal; Calvin Yeang; David Q.-H. Wang; M. Mahmood Hussain; Xian-Cheng Jiang

From the Department of Anatomy and Cell Biology (R.L., J.I., C.Y., M.M.H., X.C.J.), SUNY Downstate Medical Center, Brooklyn, NY; and the Department of Medicine, Liver Center and Gastroenterology Division (D.Q.-H.W.), Beth Israel Deaconess Medical Center, Harvard Medical School and Harvard Digestive Diseases Center, Boston, Mass.

Correspondence to M. Mahmood Hussain or Xian-Cheng Jiang, Department of Anatomy and Cell Biology, SUNY Downstate Medical Center, 450 Clarkson Ave, Box 5, Brooklyn, NY 11203. E-mail mhussain{at}downstate.edu or xjiang@downstate.edu

Objective— Phospholipid transfer protein (PLTP) plays an important role in lipoprotein metabolism and atherosclerosis. PLTP gene knockout (KO) mice show significant reduction of plasma cholesterol levels. Because small intestine is one of the major tissue expressing PLTP, we hypothesize that PLTP deficient small intestine absorbs less cholesterol, thus contributing to the diminishing of cholesterol levels in the plasma.

Methods and Results— We used dual-labeled cholesterol/sitostanol feeding approach to study cholesterol absorption in PLTP KO and WT mice. We found that PLTP KO mice absorb significant less cholesterol than WT mice. Primary enterocytes isolated from PLTP KO enterocytes took up significant less cholesterol. Moreover, we observed that Niemann-Pick C1-like 1 (NPC1L1) mRNA levels were significantly decreased in the small intestine of PLTP KO mice. Next, we studied the secretion of cholesterol by enterocytes. The amounts of cholesterol transported to plasma and liver were significantly reduced in PLTP KO mice, compared with WT animals. Studies with isolated PLTP KO enterocytes revealed that the secretion of cholesterol via chylomicron and intestinal-HDL was significantly reduced. Furthermore, ATP-binding cassette transporters (ABC) A1 mRNA and microsomal triglyceride transfer protein (MTP) activity levels were significantly decreased in PLTP KO small intestine.

Conclusion— These results indicate that PLTP deficiency results in reduced cholesterol uptake as well as secretion by the intestine. We suggest that PLTP could be a useful target to lower plasma cholesterol levels, thus reducing atherosclerosis.

PLTP deficiency results in reduced cholesterol uptake as well as secretion by the intestine. We suggest that PLTP could be a useful target to lower plasma cholesterol levels, thus reducing atherosclerosis.

Key Words: PLTP gene knockout • cholesterol absorption • intestine • enterocytes • lipoproteins

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