Novel Roles of Kallistatin, a Specific Tissue Kallikrein Inhibitor, in Vascular Remodeling
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Julie Chao
Abstract
We have purified, cloned and characterized kallistatin, a tissue kallikrein-binding protein (KBP) in humans and rodents. Kallistatin is a unique serine proteinase inhibitor (serpin) with Phe-Phe residues at the P2 and P1 positions. Structural and functional analysis of kallistatin by site-directed mutagenesis and protein engineering indicate that wild-type kallistatin is selective for tissue kallikrein. Kallistatin is expressed and localized in endothelial and smooth muscle cells of blood vessels and has multiple roles in vascular function independent of the tissue kallikrein-kinin system. First, kallistatin induces vasorelaxation of isolated aortic rings and reduces renal perfusion pressure in isolated rat kidneys. Transgenic mice overexpressing rat kallistatin are hypotensive, and adenovirus-mediated gene delivery of human kallistatin attenuates blood pressure rise in spontaneously hypertensive rats. Second, kallistatin stimulates the proliferation and migration of vascular smooth muscle cells in vitro and neointima formation in balloon-injured rat arteries. Third, kallistatin inhibits the proliferation, migration and adhesion of endothelial cells in vitro and angiogenesis in the rat model of hindlimb ischemia. These results demonstrate novel roles of kallistatin in blood pressure regulation and vascular remodeling.
Copyright © 2001 by Walter de Gruyter GmbH & Co. KG
Articles in the same Issue
- To Our Authors, Readers and Subscribers
- Kinins 1925-2000
- The Expanded Human Kallikrein (KLK) Gene Family: Genomic Organisation, Tissue-Specific Expression and Potential Functions
- Novel Roles of Kallistatin, a Specific Tissue Kallikrein Inhibitor, in Vascular Remodeling
- Signal Transduction from Bradykinin, Angiotensin, Adrenergic and Muscarinic Receptors to Effector Enzymes, Including ADP-Ribosyl Cyclase
- Classification of Kinin Receptors
- Metabolism-Resistant Bradykinin Antagonists: Development and Applications
- Kinins, Receptors, Kininases and Inhibitors Where Did They Lead Us?
- Bradykinin Signalling to MAP Kinase: Cell-Specific Connections versus Principle Mitogenic Pathways
- Kinins and Epithelial Ion Transport in the Alimentary Tract
- Role of the Renal Kallikrein-Kinin System in the Development of Salt-Sensitive Hypertension
- Role of the Light Chain of High Molecular Weight Kininogen in Adhesion, Cell-Associated Proteolysis and Angiogenesis
- Activation of the Kinin-Forming Cascade on the Surface of Endothelial Cells
- Kallikrein and Kinin Receptor Expression in Inflammation and Cancer
- Altered Neutrophil Homeostasis in Kinin B1 Receptor-Deficient Mice
- Cystatins as Calpain Inhibitors: Engineered Chicken Cystatin- and Stefin B-Kininogen Domain 2 Hybrids Support a Cystatin-Like Mode of Interaction with the Catalytic Subunit of µ-Calpain
- Synthetic Peptides and Fluorogenic Substrates Related to the Reactive Site Sequence of Kunitz-Type Inhibitors Isolated from Bauhinia: Interaction with Human Plasma Kallikrein
- Identification and Characterization of an Aromatic Amino Acid Decarboxylase from the Filarial Nematode, Dirofilaria immitis
- Molecular Cloning and Pharmacological Characterization of the Canine B1 and B2 Bradykinin Receptors
- Ligand-Mediated Regulation of Kinin Receptors in the Rabbit
- Activation of Sphingosine Kinase by the Bradykinin B2 Receptor and Its Implication in Regulation of the ERK/MAP Kinase Pathway
Articles in the same Issue
- To Our Authors, Readers and Subscribers
- Kinins 1925-2000
- The Expanded Human Kallikrein (KLK) Gene Family: Genomic Organisation, Tissue-Specific Expression and Potential Functions
- Novel Roles of Kallistatin, a Specific Tissue Kallikrein Inhibitor, in Vascular Remodeling
- Signal Transduction from Bradykinin, Angiotensin, Adrenergic and Muscarinic Receptors to Effector Enzymes, Including ADP-Ribosyl Cyclase
- Classification of Kinin Receptors
- Metabolism-Resistant Bradykinin Antagonists: Development and Applications
- Kinins, Receptors, Kininases and Inhibitors Where Did They Lead Us?
- Bradykinin Signalling to MAP Kinase: Cell-Specific Connections versus Principle Mitogenic Pathways
- Kinins and Epithelial Ion Transport in the Alimentary Tract
- Role of the Renal Kallikrein-Kinin System in the Development of Salt-Sensitive Hypertension
- Role of the Light Chain of High Molecular Weight Kininogen in Adhesion, Cell-Associated Proteolysis and Angiogenesis
- Activation of the Kinin-Forming Cascade on the Surface of Endothelial Cells
- Kallikrein and Kinin Receptor Expression in Inflammation and Cancer
- Altered Neutrophil Homeostasis in Kinin B1 Receptor-Deficient Mice
- Cystatins as Calpain Inhibitors: Engineered Chicken Cystatin- and Stefin B-Kininogen Domain 2 Hybrids Support a Cystatin-Like Mode of Interaction with the Catalytic Subunit of µ-Calpain
- Synthetic Peptides and Fluorogenic Substrates Related to the Reactive Site Sequence of Kunitz-Type Inhibitors Isolated from Bauhinia: Interaction with Human Plasma Kallikrein
- Identification and Characterization of an Aromatic Amino Acid Decarboxylase from the Filarial Nematode, Dirofilaria immitis
- Molecular Cloning and Pharmacological Characterization of the Canine B1 and B2 Bradykinin Receptors
- Ligand-Mediated Regulation of Kinin Receptors in the Rabbit
- Activation of Sphingosine Kinase by the Bradykinin B2 Receptor and Its Implication in Regulation of the ERK/MAP Kinase Pathway
