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What is Plasma Kallikrein?
Plasma kallikrein is a vascular serine protease, circulating in blood as an inactive zymogen, prekallikrein. Upon activation, plasma kallikrein cleaves its physiological substrate high molecular weight kininogen, generating the potent inflammatory vasodilator peptide bradykinin. Binding of bradykinin to its receptors on the surface of endothelial cells lining blood vessels initiates a series of signaling events leading to the opening of intercellular junctions between endothelial cells, resulting in increased vascular permeability.
Plasma Kallikrein & Edema
Plasma kallikrein is a known mediator of edema formation in human disease; uncontrolled activation of plasma kallikrein, caused by deficiency of its physiological inhibitor (C1-Inhibitor) in the rare genetic disease hereditary angioedema (HAE), results in acute systemic edema.
Plasma Kallikrein in Diabetes
Prekallikrein levels in diabetics have been correlated with hypertension and hyperglycemia, the major risk factors for development of DME. Elevated prekallikrein levels are found in individuals with diabetic retinopathy, and in the vitreous of DME patients. Importantly, activation of prekallikrein in vivo has been shown to result in increased retinal vascular permeability, the primary cause of DME.
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