title: An emerging role of degrading proteinases in hypertension and the metabolic syndrome: autodigestion and receptor cleavage.
abstract: One of the major challenges for hypertension research is to identify the mechanisms that cause the comorbidities encountered in many hypertensive patients, as seen in the metabolic syndrome. An emerging body of evidence suggests that human and experimental hypertensives may exhibit uncontrolled activity of proteinases, including the family of matrix metalloproteinases, recognized for their ability to restructure the extracellular matrix proteins and to play a role in hypertrophy. We propose a new hypothesis that provides a molecular framework for the comorbidities of hypertension, diabetes, capillary rarefaction, immune suppression, and other cell and organ dysfunctions due to early and uncontrolled extracellular receptor cleavage by active proteinases. The proteinase and signaling activity in hypertensives requires further detailed analysis of the proteinase expression, the mechanisms causing proenzyme activation, and identification of the proteinase substrate. This work may open the opportunity for reassessment of old interventions and development of new interventions to manage hypertension and its comorbidities.
authors.affiliation: Department of Bioengineering, Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA 92093-0412, USA. gwss@ucsd.edu
authors.forename: Geert W
authors.initials: GW
authors.lastname: Schmid-Schönbein
mesh_terms: D015897:Comorbidity; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000201:enzymology* / Q000503:physiopathology; D006984:Hypertrophy / Q000201:enzymology; D007108:Immune Tolerance / Q000502:physiology; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D024821:Metabolic Syndrome / Q000150:complications / Q000201:enzymology* / Q000503:physiopathology; D008833:Microcirculation / Q000502:physiology; D008954:Models, Biological; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D016326:Extracellular Matrix Proteins; D011956:Receptors, Cell Surface; D020782:Matrix Metalloproteinases
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