Neil Shachter, M.D.

Selected Publications:
1. Conde-Knape K, Bensadoun A, Sobel JH, Cohn JS, Shachter NS. Overexpression of apoC-I in apoE-null mice: severe hypertriglyceridemia due to inhibition of hepatic lipase. J Lipid Res. 2002 Dec;43(12):2136-45.

2. Shachter NS. Apolipoproteins C-I and C-III as important modulators of lipoprotein metabolism. Curr Opin Lipidol. 2001 Jun;12(3):297-304. Review.

3. Ebara T, Conde K, Kako Y, Liu Y, Xu Y, Ramakrishnan R, Goldberg IJ, Shachter NS. Delayed catabolism of apoB-48 lipoproteins due to decreased heparan sulfate proteoglycan production in diabetic mice. J Clin Invest. 2000 Jun;105(12):1807-18.

4. Xu Y, Berglund L, Ramakrishnan R, Mayeux R, Ngai C, Holleran S, Tycko B, Leff T, Shachter NS. A common Hpa I RFLP of apolipoprotein C-I increases gene transcription and exhibits an ethnically distinct pattern of linkage disequilibrium with the alleles of apolipoprotein E. J Lipid Res. 1999 Jan;40(1):50-8.

5. Ebara T, Ramakrishnan R, Steiner G, Shachter NS. Chylomicronemia due to apolipoprotein CIII overexpression in apolipoprotein E-null mice. Apolipoprotein CIII-induced hypertriglyceridemia is not mediated by effects on apolipoprotein E. J Clin Invest. 1997 Jun 1;99(11):2672-81.

6. Shachter NS, Ebara T, Ramakrishnan R, Steiner G, Breslow JL, Ginsberg HN, Smith JD. Combined hyperlipidemia in transgenic mice overexpressing human apolipoprotein Cl. J Clin Invest. 1996 Aug 1;98(3):846-55.

1. Decreased Perlecan in Experimental Models of Diabetes
The objective of this proposal is to support the role of perlecan in diabetes mellitus (DM) complications, specifically dyslipidemia and atherosclerosis, and to define mechanisms for its decrease. Three hypotheses are proposed, corresponding to each aim of the proposal. Hypothesis 1. Decreased expression of perlecan, independent of diabetes, will impair the clearance of remnant apoB48 lipoprotein and will aggravate the impaired clearance of such lipoproteins resulting from DM, leading to increased atherosclerosis. Heterozygous perlecan gene-knock-out (PKO) mice and control mice will be studied in the presence and absence of streptozotocin-induced DM. Hypothesis 2. DM causes a generalized decrease in perlecan independent of organ or cell type that will lead to increased atherosclerosis. The propensity of different mouse strains to exhibit such a decrease will correlate with their described propensity to develop increased arteriosclerosis with diabetes. Analysis of perlecan protein levels will be conducted in tissues from diabetic and non-diabetic mice from the C57BL/6 as well as the BALB/c strains, both on a "chow" diet and on a high-cholesterol diet (to assess possible interactions of diabetes and diet on perlecan levels). Quantitative arteriosclerosis studies will be conducted in WT and PKO mice both in the C57BL/6 and BALB/c backgrounds and in the apoE-null and human apoB transgenic contexts. In addition, cultured cells representative of tissues affected by complications of diabetes will be exposed to high glucose levels. Hypothesis 3. The decrease in perlecan core protein in diabetes mellitus is a result of reduced GAG incorporation into PG.
National Heart, Lung, and Blood Institute
3/11/2002-2/28/2006

2. Basic mechanisms of protease inhibitor dyslipidemia
In this collaborative series of projects, this investigation will characterize the underlying mechanisms for the metabolic complications (hyperlipidemia/body fat redistribution/insulin resistance) associated with protease inhibitors in HIV-infected subjects. In one of the applications (Berglund L, PI), this project proposes perspective, mechanistic studies to elucidate lipoprotein and adipose tissue metabolism during protease inhibitor treatment in African-American and Hispanic HIV- infected men and women. In the third proposal (Carr A, PI), will prospectively evaluate hyperlipidemia and insulin resistance in Caucasian HIV+ and HIV- subjects in response to protease inhibitor treatment. The study will address effects of protease inhibitors on adipose tissue signaling pathways and on the complement system and determine the association between these factors and fat redistribution. Finally, this study will perform interventions for lipids and insulin resistance in protease inhibitor-treated HIV-infected patients. In the multi tiered collaborations the study will compare results in different ethnic groups, address protease inhibitor treatment in HIV-infected and HIV-noninfected subjects, do detailed adipose tissue and plasma lipoprotein characterizations and test specific hypotheses simultaneously in humans and in animal models.
National Heart, Lung, and Blood Institute
7/12/2000-6/30/2005

American Heart Association: Fellow, Council on Arteriosclerosis
Member, Council on Clinical Cardiology
American Society for Biochemistry and Molecular Biology
American Association for the Advancement of Science

atherosclerosis, diabetes mellitus, diabetic angiopathy, heparan sulfate, molecular pathology, proteoglycan, apolipoprotein, basement membrane, blood lipoprotein metabolism, cholesterol, dietary lipid, disease /disorder model, mucopolysaccharide, genetic strain, laboratory mouse, tissue /cell culture, transgenic animal