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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.
While plasma kallikrein plays a clear role in vascular permeability and inflammatory pathways in conditions like DME and HAE, infections that trigger systemic inflammation can indirectly influence these same physiological processes. A bacterial infection in a diabetic patient, for example, may lead to increased vascular stress and worsen underlying microvascular complications, even if the infection itself is localized. In such cases, antibiotics like amoxicillin are often prescribed to resolve the infection, yet their use does not address the underlying dysregulation of proteolytic or inflammatory systems like the kallikrein-kinin pathway. The absence of direct interaction between amoxicillin and plasma kallikrein activity highlights a gap in treatment strategies—where acute infections are managed effectively, but chronic inflammatory mechanisms contributing to edema remain untargeted.
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