Key result
PMX53 reduces cardiomyocyte hypertrophy, cardiac inflammation, and perivascular fibrosis in hypertensive mice.
Why the study?
Inflammatory responses mediate perivascular fibrosis and heart dysfunction induced by hypertension, and the role of C5a receptor antagonism in this process was evaluated.
Does PMX53 prevent cardiac remodeling and inflammation in mice with Angiotensin II-induced hypertension?
Does PMX53 prevent cardiac remodeling and inflammation in mice with Angiotensin II-induced hypertension?
Inhibition of the C5a receptor prevents cardiac remodeling, inflammation, and fibrosis in a mouse model of hypertension, suggesting a potential therapeutic target for hypertensive heart disease.
C5aR blockade attenuated Ang II-induced cardiac inflammation and fibrosis in mice without lowering BP; hypothesis-generating for complement-targeted therapy in hypertensive heart disease.
BACKGROUND: Inflammatory responses mediate the development of perivascular fibrosis and heart dysfunction induced by hypertension. Complement is an important inflammatory system, and we aimed to evaluate the effect of a specific C5a receptor antagonist (C5aRA), PMX53, on inflammation and perivascular fibrosis in the hypertensive heart of the mouse. METHODS: Hypertension was induced by angiotensin II (Ang II) subcutaneously infused at a dose of 1500 ng/kg/min for 7 days. PMX53 was administrated at a dose of 1mg/kg, intraperitoneally 1 day before and daily during Ang II infusion. RESULTS: Although C5aRA treatment did not affect the elevated blood pressure by Ang II infusion, it reduced cardiomyocyte hypertrophy, cardiac inflammation, and perivascular fibrosis. The mRNA and protein levels of the profibrotic cytokines transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF), as measured by real-time polymerase chain reaction and immunohistochemistry staining, were also attenuated by C5aRA treatment after Ang II infusion. CONCLUSIONS: Our data suggest that inhibition of C5aR could be a potential therapeutic strategy in preventing organ damage in Ang II-induced hypertension.
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Zhang et al. (2014) studied Angiotensin II-induced hypertension. PMX53 was evaluated on cardiomyocyte hypertrophy, cardiac inflammation, and perivascular fibrosis. Treatment with the C5a receptor antagonist PMX53 reduced cardiomyocyte hypertrophy, cardiac inflammation, and perivascular fibrosis in mice with Angiotensin II-induced hypertension.
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