Asian Science Citation Index is committed to provide an authoritative, trusted and significant information by the coverage of the most important and influential journals to meet the needs of the global scientific community.  
ASCI Database
308-Lasani Town,
Sargodha Road,
Faisalabad, Pakistan
Fax: +92-41-8815544
Contact Via Web
Suggest a Journal
Articles by Y. t Shen
Total Records ( 3 ) for Y. t Shen
  S Bhashyam , A. V Fields , B Patterson , J. M Testani , L Chen , Y. t Shen and R. P. Shannon

We have shown that glucagon-like peptide-1 (GLP-1[7–36] amide) stimulates myocardial glucose uptake in dilated cardiomyopathy (DCM) independent of an insulinotropic effect. The cellular mechanisms of GLP-1–induced myocardial glucose uptake are unknown.

Methods and Results—

Myocardial substrates and glucoregulatory hormones were measured in conscious, chronically instrumented dogs at control (n=6), DCM (n=9) and DCM after treatment with a 48-hour infusion of GLP-1 (7–36) amide (n=9) or vehicle (n=6). GLP-1 receptors and cellular pathways implicated in myocardial glucose uptake were measured in sarcolemmal membranes harvested from the 4 groups. GLP-1 stimulated myocardial glucose uptake (DCM: 20±7 nmol/min/g; DCM+GLP-1: 61±12 nmol/min/g; P=0.001) independent of increased plasma insulin levels. The GLP-1 receptors were upregulated in the sarcolemmal membranes (control: 98±2 density units; DCM: 256±58 density units; P=0.046) and were expressed in their activated (65 kDa) form in DCM. The GLP-1–induced increases in myocardial glucose uptake did not involve adenylyl cyclase or Akt activation but was associated with marked increases in p38 MAP kinase activity (DCM+vehicle: 97±22 pmol ATP/mg/min; DCM+GLP-1: 170±36 pmol ATP/mg/min; P=0.051), induction of nitric oxide synthase 2 (DCM+vehicle: 151±13 density units; DCM+GLP-1: 306±12 density units; P=0.001), and GLUT-1 translocation (DCM+vehicle: 21±3% membrane bound; DCM+GLP-1: 39±3% membrane bound; P=0.005). The effects of GLP-1 on myocardial glucose uptake were blocked by pretreatment with the p38 MAP kinase inhibitor or the nonspecific nitric oxide synthase inhibitor nitro-l-arginine.


GLP-1 stimulates myocardial glucose uptake through a non–Akt-1–dependent mechanism by activating cellular pathways that have been identified in mediating chronic hibernation and the late phase of ischemic preconditioning.

  Y. T Shen , F. I Malik , X Zhao , C Depre , S. K Dhar , P Abarzua , D. J Morgans and S. F. Vatner

Therapy for chronic systolic heart failure (sHF) has improved over the past 2 decades, but the armamentarium of drugs is limited and consequently sHF remains a leading cause of death and disability. In this investigation, we examined the effects of a novel cardiac myosin activator, omecamtiv mecarbil (formerly CK-1827452) in 2 different models of heart failure.

Methods and Results—

Two different models of sHF were used: (1) pacing-induced sHF after myocardial infarction (MI-sHF) and (2) pacing-induced sHF after 1 year of chronic pressure overload left ventricular hypertrophy (LVH-sHF). Omecamtiv mecarbil increased systolic function in sHF dogs, chronically instrumented to measure LV pressure, wall thickness, and cardiac output. Omecamtiv mecarbil, infused for 24 hours, induced a sustained increase without desensitization (P<0.05) in wall thickening (25±6.2%), stroke volume (44±6.5%) and cardiac output (22±2.8%), and decreased heart rate (15±3.0%). The major differences between the effect of omecamtiv mecarbil on cardiac function and the effect induced by a catecholamine, for example, dobutamine, is that omecamtiv mecarbil did not increase LV dP/dt but rather increased LV systolic ejection time by 26±2.9% in sHF. Another key difference is that myocardial O2 consumption (MVO2), which increases with catecholamines, was not significantly affected by omecamtiv mecarbil.


These results demonstrate that chronic infusion of the cardiac myosin activator, omecamtiv mecarbil, improves LV function in sHF without the limitations of progressive desensitization and increased MVO2. This unique profile may provide a new therapeutic approach for patients with sHF.

  C Wu , L Yan , C Depre , S. K Dhar , Y. T Shen , J Sadoshima , S. F Vatner and D. E. Vatner

Cytochrome c oxidase (COX) is composed of 13 subunits, of which COX I, II, and III are encoded by a mitochondrial gene. COX I and II function as the main catalytic components, but the function of COX III is unclear. Because myocardial ischemia affects mitochondrial oxidative metabolism, we hypothesized that COX activity and expression would be affected during postischemic cardiomyopathy. This hypothesis was tested in a monkey model following myocardial infarction (MI) and subsequent pacing-induced heart failure (HF). In this model, COX I protein expression was decreased threefold after MI and fourfold after HF (P < 0.05 vs. sham), whereas COX II expression remained unchanged. COX III protein expression increased 5-fold after MI and further increased 10-fold after HF compared with sham (P < 0.05 vs. sham). The physiological impact of COX III regulation was examined in vitro. Overexpression of COX III in mitochondria of HL-1 cells resulted in an 80% decrease in COX I, 60% decrease in global COX activity, 60% decrease in cell viability, and threefold increase in apoptosis (P < 0.05). Oxidative stress induced by H2O2 significantly (P < 0.05) increased COX III expression. H2O2 decreased cell viability by 47 ± 3% upon overexpression of COX III, but only by 12 ± 5% in control conditions (P < 0.05). We conclude that ischemic stress in vivo and oxidative stress in vitro lead to upregulation of COX III, followed by downregulation of COX I expression, impaired COX oxidative activity, and increased apoptosis. Therefore, upregulation of COX III may contribute to the increased susceptibility to apoptosis following MI and subsequent HF.

Copyright   |   Desclaimer   |    Privacy Policy   |   Browsers   |   Accessibility