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Featured researches published by Yan Ting Zhou.


Circulation | 2000

Echocardiographic Destruction of Albumin Microbubbles Directs Gene Delivery to the Myocardium

Ralph V. Shohet; Shuyuan Chen; Yan Ting Zhou; Zhuowei Wang; Robert S. Meidell; Roger H. Unger; Paul A. Grayburn

BACKGROUND The noninvasive, tissue-specific delivery of therapeutic agents to the heart would be a valuable clinical tool. This study addressed the hypothesis that albumin-coated microbubbles could be used to effectively deliver an adenoviral transgene to rat myocardium by ultrasound-mediated microbubble destruction. METHODS AND RESULTS Recombinant adenovirus containing beta-galactosidase and driven by a constitutive promoter was attached to the surface of albumin-coated, perfluoropropane-filled microbubbles. These bubbles were infused into the jugular vein of rats with or without simultaneous echocardiography. Additional controls included ultrasound of microbubbles that did not contain virus, virus alone, and virus plus ultrasound. One group underwent ultrasound-mediated destruction of microbubbles followed by adenovirus infusion. Rats were killed after 4 days and examined for beta-galactosidase expression. The hearts of all rats that underwent ultrasound-mediated destruction of microbubbles containing virus showed nuclear staining with 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside substrate, indicating expression of the transgene. None of the control animals showed myocardial expression of the beta-galactosidase transgene. By quantitative analysis, beta-galactosidase activity was 10-fold higher in the treated group than in controls (P<0.0001). CONCLUSIONS Ultrasound-mediated destruction of albumin-coated microbubbles is a promising method for the delivery of bioactive agents to the heart.


Journal of Biological Chemistry | 1998

Lipoapoptosis in beta-cells of obese prediabetic fa/fa rats. Role of serine palmitoyltransferase overexpression.

Michio Shimabukuro; Moritake Higa; Yan Ting Zhou; May Yun Wang; Christopher B. Newgard; Roger H. Unger

We reported that the lipoapoptosis of beta-cells observed in fat-laden islets of obese fa/fa Zucker Diabetic Fatty (ZDF) rats results from overproduction of ceramide, an initiator of the apoptotic cascade and is induced by long-chain fatty acids (FA). Whereas the ceramide of cytokine-induced apoptosis may be derived from sphingomyelin hydrolysis, FA-induced ceramide overproduction seems to be derived from FA. We therefore semiquantified mRNA of serine palmitoyltransferase (SPT), which catalyzes the first step in ceramide synthesis. It was 2–3-fold higher in fa/fa islets than in+/+ controls. [3H]Ceramide formation from [3H]serine was 2.2–4.5-fold higher in fa/faislets. Triacsin-C, which blocks palmitoyl-CoA synthesis, andl-cycloserine, which blocks SPT activity, completely blocked [3H]ceramide formation from [3H]serine. Islets of fa/fa rats are unresponsive to the lipopenic action of leptin, which normally depletes fat and prevents FA up-regulation of SPT. To determine the role of leptin unresponsiveness in the SPT overexpression, we transferred wild type OB-Rb cDNA to their islets; now leptin completely blocked the exaggerated FA-induced increase of SPT mRNA while reducing the fat content. Beta-cell lipoapoptosis was partially prevented in vivo by treating prediabetic ZDF rats withl-cycloserine for 2 weeks. Ceramide content and DNA fragmentation both declined 40–50%. We conclude that lipoapoptosis of ZDF rats is mediated by enhanced ceramide synthesis from FA and that blockade by SPT inhibitors prevents lipoapoptosis.


Journal of Biological Chemistry | 1997

Leptin Normalizes the Impaired Response of Proinsulin mRNA to Long Chain Fatty Acids in Heterozygous Zucker Diabetic Fatty Rats

Yan Ting Zhou; Michio Shimabukuro; Young Lee; Kazunori Koyama; Falguni Trieu; Roger H. Unger

To determine if underleptinization of islets of Zucker diabetic fatty (ZDF) rats is the proximal cause of their inability to compensate for obesity, we compared the proinsulin/β-actin mRNA ratio in heterozygous (fa/+) ZDF rats with that of wild-type (+/+) and homozygous (fa/fa) ZDF rats. In +/+ islets cultured with 2 mm free fatty acids (FFA) the proinsulin mRNA ratio rose 2.4-fold at 12 h. In fa/+ islets, the ratio rose only 65% above normal. There was no change in fa/faislets. The presence of leptin (20 ng/ml) in the culture medium increased the FFA-induced response of proinsulin mRNA offa/+ islets to that of +/+ islets while reducing FFA incorporation into triglycerides. The leptin-induced improvement in the proinsulin mRNA response was independent of any changes in glucose usage. These findings support a causal relationship between diminished leptin action on islets and the impaired β-cell response to FFA in ZDF rats.


Proceedings of the National Academy of Sciences of the United States of America | 2000

Lipotoxic heart disease in obese rats: Implications for human obesity

Yan Ting Zhou; Paul A. Grayburn; Asad Karim; Michio Shimabukuro; Moritake Higa; D. Baetens; Lelio Orci; Roger H. Unger


Proceedings of the National Academy of Sciences of the United States of America | 1998

Fatty acid-induced β cell apoptosis: A link between obesity and diabetes

Michio Shimabukuro; Yan Ting Zhou; Moshe Levi; Roger H. Unger


Proceedings of the National Academy of Sciences of the United States of America | 1999

Regulation of fatty acid homeostasis in cells: Novel role of leptin

Roger H. Unger; Yan Ting Zhou; Lelio Orci


Proceedings of the National Academy of Sciences of the United States of America | 1997

Induction by leptin of uncoupling protein-2 and enzymes of fatty acid oxidation

Yan Ting Zhou; Michio Shimabukuro; Kazunori Koyama; Young Lee; May Yun Wang; Falguni Trieu; Christopher B. Newgard; Roger H. Unger


Proceedings of the National Academy of Sciences of the United States of America | 1996

Disappearance of body fat in normal rats induced by adenovirus-mediated leptin gene therapy

Guoxun Chen; Kazunori Koyama; Xue Yuan; Young Lee; Yan Ting Zhou; Robert M. O'Doherty; Christopher B. Newgard; Roger H. Unger


Journal of Biological Chemistry | 2001

Liporegulation in Diet-induced Obesity THE ANTISTEATOTIC ROLE OF HYPERLEPTINEMIA

Young Lee; May Yun Wang; Tetsuya Kakuma; Zhuo Wei Wang; Evelyn E. Babcock; Kay McCorkle; Moritake Higa; Yan Ting Zhou; Roger H. Unger


Proceedings of the National Academy of Sciences of the United States of America | 1999

Reversing adipocyte differentiation: Implications for treatment of obesity

Yan Ting Zhou; Zhuo Wei Wang; Moritake Higa; Christopher B. Newgard; Roger H. Unger

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Roger H. Unger

University of Texas Southwestern Medical Center

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Young Lee

University of Texas Southwestern Medical Center

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Moritake Higa

University of Texas Southwestern Medical Center

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May Yun Wang

University of Texas Southwestern Medical Center

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Kazunori Koyama

University of Texas Southwestern Medical Center

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Zhuo Wei Wang

University of Texas Southwestern Medical Center

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Tetsuya Kakuma

University of Texas Southwestern Medical Center

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