| Summary: | 碩士 === 國立成功大學 === 生理學研究所 === 97 === Peroxisome proliferator-activated receptor gamma (PPARgamma) is the nuclear receptor that regulates adipocyte development and glucose homeostasis. Loss-of-function mutations in the PPARgamma gene are implicated in human hypertension and PPARgamma agonists decrease blood pressure both in animal models and in human patients. How PPARgamma affects blood pressure and vascular reactivity is still unclear in vivo. To study the role of PPARgamma in the pathogenesis of hypertension and vascular diseases, we generated mice with extremely low PPARgamma level. Our previous data showed that mice with low PPARgamma level exhibited increased systolic blood pressure without significant change in diastolic blood pressure, resulting in a significant increase of pulse pressure. The loss of elasticity of the aorta, generally termed aortic stiffness, is thought to be one of the most important factors in the development of increased pulse pressure. Thus, we hypothesized that PPARgamma deficiency caused aortic stiffness, resulting in the increase in pulse pressure. First, we found that aortic pulse wave velocity (PWV), a non-invasive assessment of aortic stiffness, was significantly increased in PPARgamma hypomorphic mice, suggesting the aortas of PPARgamma hypomorphic mice were stiffer than wild-type mice. The expression of elastin, a prominent structural protein contributing to aortic distensibility, was significantly decreased in aortas of PPARgamma hypomorphic mice. Furthermore, the elastin expression was negatively correlated with aortic PWV in PPARgamma hypomorphic mice. In addition, the expression of matrix metalloproteinase-9 (MMP-9), which is reported to be able to break down elastin and involved in the process of arterial stiffening, was significantly increased in aortas of PPARgamma hypomorphic mice. The elevated PWV in PpargC/- mice was ameliorated after treatment of PPARgamma agonist, which was associated with attenuated expressions of decreased elastin and increased MMP-9. Together, our results suggest that PPARgamma deficiency causes loss of elasticity in aorta and development of aortic stiffness, further resulting in elevated pulse pressure. This study underscores the importance of PPARgamma in the regulation of blood pressure and vascular reactivity.
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