Proteolytic degradation and receptor cleavage in the microcirculation
Geert W. SCHMID-SCHÖNBEIN Department of Bioengineering Institute of Engineering in Medicine University of California San Diego La Jolla California, 92093-0412 ABSTRACT We propose here a previously unrecognized pathogenic mechanism for hypertension and diabetes and the cluster of multifaceted cell dysfunctions characteristic of the metabolic syndrome. The evidence for this new hypothesis is derived from a genetic model with unchecked proteolytic activity, including that of matrix metalloproteinases, which causes cleavage of the extracellular domain of surface receptors and loss of their respective functions. For example, cleavage of the extracellular domain of the β2-adrenergic receptor promotes arteriolar vasoconstriction and elevates central blood…