Childhood Factors for Young Adult Aortic Stiffness (p 1133)
Arterial stiffness measured as aortic pulse wave velocity (PWV) is among the most powerful indicator of prognosis, independent of blood pressure. In this issue’s article on the third but pilot follow-up of 21–23 years olds (MRC DASH study) previously seen twice as schoolchildren in London, United Kingdom, for a given level of blood pressure some people had stiffer blood vessels than others, even as young adults (Figure). The cohort is purposefully multiethnic; intriguingly, ethnic groups whose parents’ generations are at greater cardiovascular risk, PWV was on average lower than that in Europeans.
Although abdominal adiposity (as measured by waist/height ratio) in 11 to 13 years old predicted lower PWV, it was associated with higher PWV when they were 21 to 23 years old. Measured physical activity, particularly more than moderate, was measured in a subsample and was associated with lower, better, PWV.
These data suggest that understanding the dynamics of how major vessels stiffen during growth and young adult life and transmit the pressure or pulse wave too vigorously to tissues offer mechanistic, therapeutic, and public health opportunities for improving cardiovascular function.
Peroxisome Proliferator–Activated Receptor-γ Regulates Elastogenesis (p 1298)
Loss of integrity and massive disruption of elastic architecture are key features in abdominal aortic aneurysm (AAA). Using a moderate dose of angiotensin II infusion into mice, we determined that expression >50% of peroxisome proliferator–activated receptor-γ (PPARγ) is critical for maintaining normal elastic waviness of elastic fibers (Figure). Further reduction to 25% normal expression (PpargC/−) caused elastic fiber breakdown at the modest angiotensin II and suprarenal aortic aneurysms at a higher dose of angiotensin II infusion. These data indicate that decreased Pparg expression is a novel risk factor for hypertension-related AAA. Reduced Pparg expression was paralleled with a significant reduction in the expression of vital elastic fiber components, elastin, and fibulin-5. The regulatory role of PPARγ in elastogenesis takes place in fibroblasts by binding the genomic sequence of Fbln5. Together, our study highlights PPARγ as a vital regulator in elastogenesis and AAA development and suggests that genetic variants affecting PPARγ levels would be important for identifying patients at a higher risk for developing AAA. Furthermore, pharmacological intervention targeting PPARγ level/activity would be beneficial to preserve elastic fiber integrity during AAA initiation and development.
Preeclampsia: Myocardial Dysfunction (p 1273)
Hypertensive disorders of pregnancy (HDP) are associated with cardiac dysfunction. Antiangiogenic proteins have been implicated in the pathogenesis of HDP. Here, we report in a prospective cohort study that plasma levels of soluble fms-tyrosine kinase-1 and soluble endoglin, both antiangiogenic proteins elevated in preeclampsia, independently correlate with cardiac dysfunction markers measured using global longitudinal strain on cardiac echocardiography. Furthermore, the association of these biomarkers with worse left ventricular strain persisted after adjusting for mean arterial pressure, thus indicating an independent role for antiangiogenic proteins in inducing cardiac dysfunction. Taken together with previous experimental studies suggesting that soluble fms-tyrosine kinase-1 administration in pregnant animals causes cardiac dysfunctions similar to what is noted in humans with preeclampsia, our data support a causal role for soluble fms-tyrosine kinase-1 in mediating cardiac dysfunction noted in subjects with HDP. Additional studies are needed to evaluate whether targeting antiangiogenic proteins during HDP may lead to improvement of myocardial function during HDP. Further work should determine whether altered levels in antiangiogenic protein levels are persistent and contribute to cardiovascular disease in the long-term.
- © 2016 American Heart Association, Inc.