Loss of CD47 Attenuates Angiotensin II Mediated Hypertension

Abstract

CD47 plays a role in vascular reactivity by inhibiting both nitric oxide (NO) production and signaling. Because altered NO signaling is implicated in cardiovascular disease and hypertension, we explored the role of CD47 in the development of angiotensin II (AngII) mediated hypertension. In anesthetized CD47‐/‐ mice, AngII injection failed to elicit the increase in blood pressure seen in a WT mouse. Expression of the AT1R receptor was measured in homogenized vessels via Western blotting, and it was determined that levels were not significantly different between WT and knockout animals, suggesting decreased response was not due to lack of receptor availability. To further characterize this lack of response, isolated TDAs from both WT and CD47‐/‐ mice were cannulated and pressurized. Vessel diameter was assessed in response to increasing doses of AngII. Unexpectedly, we found that vessels from CD47‐/‐ mice displayed decreased sensitivity to AngII‐mediated vasoconstriction compared to WT vessels. Constriction to KCl was similar in vessels from WT and CD47‐/‐ animals, demonstrating that the contractile mechanism was still fully intact in the knockout animal. Taken together, this data suggests CD47 is important for AngII‐mediated vasoconstriction and therefore has the ability to effect systemic tone and blood pressure. We are actively investigating the molecular mechanisms governing this relationship, and plan to explore blood pressure in conscious animals via radiotelemetry units as well as whether germ line CD47 deletion and therapeutic blockade of CD47 protects against AngII‐induced organ remodeling in the heart and kidneys.Source: NIH R00 HL‐11290402, NIH R01 HL‐108954