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An Emerging Role of Degrading Proteinases in Hypertension and the Metabolic Syndrome: Autodigestion and Receptor Cleavage

  • Pathogenesis of Hypertension: Genetic and Environmental Factors (DT O’Connor, Section Editor)
  • Published:
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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.

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Funding

NIH Grant HL 10881 and an unrestricted research gift from Leading Ventures.

Disclosure

Dr. Schmid-Schönbein is scientific advisor to Leading Ventures and owns interest in InhibeX, a company by Leading Ventures.

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  1. Department of Bioengineering, Institute of Engineering in Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0412, USA

    Geert W. Schmid-Schönbein

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Schmid-Schönbein, G.W. An Emerging Role of Degrading Proteinases in Hypertension and the Metabolic Syndrome: Autodigestion and Receptor Cleavage. Curr Hypertens Rep 14, 88–96 (2012). https://doi.org/10.1007/s11906-011-0240-9

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