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 has been shown to result in increased retinal vascular
permeability, the primary cause of DME.
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