Judy Y Lin

Publications of Judy Y Lin

• Pathogenetic role of eNOS uncoupling in cardiopulmonary disorders.

  Authors: Jan F Gielis, Judy Y Lin, Kirstin Wingler, Paul E Y Van Schil, Harald H Schmidt, An L Moens

  Free radical biology & medicine. 04/2011; 50(7):765-76.

  The homodimeric flavohemeprotein endothelial nitric oxide synthase (eNOS) oxidizes l-arginine to l-citrulline and nitric oxide (NO), which acutely vasodilates blood vessels and inhibits plateletThe homodimeric flavohemeprotein endothelial nitric oxide synthase (eNOS) oxidizes l-arginine to l-citrulline and nitric oxide (NO), which acutely vasodilates blood vessels and inhibits platelet aggregation. Chronically, eNOS has a major role in the regulation of blood pressure and prevention of atherosclerosis by decreasing leukocyte adhesion and smooth muscle proliferation. However, a disturbed vascular redox balance results in eNOS damage and uncoupling of oxygen activation from l-arginine conversion. Uncoupled eNOS monomerizes and generates reactive oxygen species (ROS) rather than NO. Indeed, eNOS uncoupling has been suggested as one of the main pathomechanisms in a broad range of cardiovascular and pulmonary disorders such as atherosclerosis, ventricular remodeling, and pulmonary hypertension. Therefore, modulating uncoupled eNOS, in particular eNOS-dependent ROS generation, is an attractive therapeutic approach to preventing and/or treating cardiopulmonary disorders, including protective effects during cardiothoracic surgery. This review provides a comprehensive overview of the pathogenetic role of uncoupled eNOS in both cardiovascular and pulmonary disorders. In addition, the related therapeutic possibilities such as supplementation with the eNOS substrate l-arginine, volatile NO, and direct NO donors as well as eNOS modulators such as the eNOS cofactor tetrahydrobiopterin and folic acid are discussed in detail.

• Targeting endothelial and myocardial dysfunction with tetrahydrobiopterin.

  Authors: An L Moens, Rinrada Kietadisorn, Judy Y Lin, David Kass

  Journal of molecular and cellular cardiology. 03/2011; 51(4):559-63.

  Tetrahydrobiopterin (BH(4)) is an essential cofactor for aromatic amino acid hydroxylases and for all three nitric oxide synthase (NOS) isoforms. It also has a protective role in the cell as anTetrahydrobiopterin (BH(4)) is an essential cofactor for aromatic amino acid hydroxylases and for all three nitric oxide synthase (NOS) isoforms. It also has a protective role in the cell as an antioxidant and scavenger of reactive nitrogen and oxygen species. Experimental studies in humans and animals demonstrate that decreased BH(4)-bioavailability, with subsequent uncoupling of endothelial NOS (eNOS) plays an important role in the pathogenesis of endothelial dysfunction, hypertension, ischemia-reperfusion injury, and pathologic cardiac remodeling. Synthetic BH(4) is clinically approved for the treatment of phenylketonuria, and experimental studies support its capacity for ameliorating cardiovascular pathophysiologies. To date, however, the translation of these studies to human patients remains limited, and early results have been mixed. In this review, we discuss the pathophysiologic role of decreased BH(4) bioavailability, molecular mechanisms regulating its metabolism, and its potential therapeutic use as well as pitfalls as an NOS-modulating drug. This article is part of a special issue entitled ''Key Signaling Molecules in Hypertrophy and Heart Failure.''

• Tetrahydrobiopterin and hypertension: more than an emigrating story.

  Authors: Judy Y Lin, An L Moens

  American journal of physiology. Heart and circulatory physiology. 01/2011; 300(3):H715.

  n/a.

• Lung ischemia-reperfusion injury: a molecular and clinical view on a complex pathophysiological process.

  Authors: Willem A den Hengst, Jan F Gielis, Judy Y Lin, Paul E Van Schil, Leon J De Windt, An L Moens

  American journal of physiology. Heart and circulatory physiology. 11/2010; 299(5):H1283-99.

  Lung ischemia-reperfusion injury remains one of the major complications after cardiac bypass surgery and lung transplantation. Due to its dual blood supply system and the availability of oxygen fromLung ischemia-reperfusion injury remains one of the major complications after cardiac bypass surgery and lung transplantation. Due to its dual blood supply system and the availability of oxygen from alveolar ventilation, the pathogenetic mechanisms of ischemia-reperfusion injury in the lungs are more complicated than in other organs, where loss of blood flow automatically leads to hypoxia. In this review, an extensive overview is given of the molecular and cellular mechanisms that are involved in the pathogenesis of lung ischemia-reperfusion injury and the possible therapeutic strategies to reduce or prevent it. In addition, the roles of neutrophils, alveolar macrophages, cytokines, and chemokines, as well as the alterations in the cell-death related pathways, are described in detail.

• Pathogenetic role of eNOS uncoupling in cardiopulmonary disorders

  Authors: Jan F. Gielis, Judy Y. Lin, Kirstin Wingler, Paul E.Y. Van Schil, Harald H. Schmidt, An L. Moens

  Free Radical Biology and Medicine.

  The homodimeric flavohemeprotein endothelial nitric oxide synthase (eNOS) oxidizes l-arginine to l-citrulline and nitric oxide (NO), which acutely vasodilates blood vessels and inhibits plateletThe homodimeric flavohemeprotein endothelial nitric oxide synthase (eNOS) oxidizes l-arginine to l-citrulline and nitric oxide (NO), which acutely vasodilates blood vessels and inhibits platelet aggregation. Chronically, eNOS has a major role in the regulation of blood pressure and prevention of atherosclerosis by decreasing leukocyte adhesion and smooth muscle proliferation. However, a disturbed vascular redox balance results in eNOS damage and uncoupling of oxygen activation from l-arginine conversion. Uncoupled eNOS monomerizes and generates reactive oxygen species (ROS) rather than NO. Indeed, eNOS uncoupling has been suggested as one of the main pathomechanisms in a broad range of cardiovascular and pulmonary disorders such as atherosclerosis, ventricular remodeling, and pulmonary hypertension. Therefore, modulating uncoupled eNOS, in particular eNOS-dependent ROS generation, is an attractive therapeutic approach to preventing and/or treating cardiopulmonary disorders, including protective effects during cardiothoracic surgery. This review provides a comprehensive overview of the pathogenetic role of uncoupled eNOS in both cardiovascular and pulmonary disorders. In addition, the related therapeutic possibilities such as supplementation with the eNOS substrate l-arginine, volatile NO, and direct NO donors as well as eNOS modulators such as the eNOS cofactor tetrahydrobiopterin and folic acid are discussed in detail.