CRP Levels Modulate Hypertension in Mouse Model

Researchers have found that C-reactive protein (CRP), a protein biomarker commonly assayed as a predictor of hypertension and other forms of cardiovascular disease, actually plays a role in the development of hypertension.

Investigators at the University of Texas Southwestern Medical School (Dallas, USA) worked with a population of mice that had been genetically engineered to express a rabbit gene for CRP synthesis. Mice of the same strain without the rabbit gene formed the control group. The rabbit gene was under regulatory control of the mouse phosphoenolpyruvate carboxykinase promoter gene that in turn was responsive to changes in dietary carbohydrate intake. Altering the animals' diets modulated production of CRP by their livers. Throughout the study conscious blood pressure (BP) measurements were performed by radiotelemetry.

Results published in the February 2007 issue of Circulation revealed that compared with controls, the engineered mice had hypertension that was predominantly systolic, and the severity of hypertension varied in parallel with changes in CRP levels modulated by dietary manipulation. The mice were shown to be sensitive to angiotensin II, which is a major circulating factor regulating blood pressure via arterial constriction. This was due to alterations in key proteins in the vascular wall that are regulated by angiotensin II.

"We found that when we switched on the gene that causes increases in CRP, the blood pressure went up, and when we turned off the gene and CRP levels went down, the blood pressure fell. Diet changes in the control mice had no effect, indicating that the blood pressure responses were due to CRP,” said senior author Dr. Wanpen Vongpatanasin, associate professor of internal medicine at the University of Texas Southwestern Medical. "Whether these same processes are operative in humans is yet to be determined. We are also pursuing follow-up studies to further understand better how CRP causes the high blood pressure in the mice.”


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University of Texas Southwestern Medical School