Aim: Atherosclerotic renovascular disease (ARVD) may impair renal function and increase cardiovascular morbidity and mortality, but the mechanism by which ARVD impacts cardiovascular function is unclear. We tested the hypothesis that preservation of renal function can reverse cardiac dysfunction in ARVD. Methods and results: Endothelial progenitor cells (EPC) were injected intra-renally (ARVD. +. EPC) after 6 weeks of swine ARVD (concurrent hypercholesterolemia and renovascular hypertension), and single-kidney function and myocardial blood-flow and microvascular permeability (MP) responses to adenosine were assessed using CT 4 weeks later. Myocardial microvascular density was evaluated by micro-CT. Inflammation and oxidative-stress were assessed in kidney venous and systemic blood samples. Normal and untreated ARVD pigs served as controls.Blood pressure was similarly increased in ARVD and ARVD. +. EPC. Compared to normal, ARVD showed lower glomerular filtration rate, elevated renal vein and systemic oxidized LDL (ox-LDL), aldosterone, uric acid, isoprostanes, transforming growth factor (TGF)-β, and interleukine-6. Renal vein ox-LDL and TGF-β showed a positive gradient across the stenotic kidney, indicating increased renal oxidative stress and fibrogenic activity. Furthermore, ARVD impaired myocardial blood-flow and MP response to adenosine, decreased microvascular density, and induced myocardial fibrosis. Improvement of renal function in ARVD. +. EPC decreased systemic aldosterone, inflammation, and oxidative stress, and improved myocardial microvascular integrity and density. Conclusion: Selective improvement in renal function, which reduced renal and systemic oxidative stress and inflammation, preserved remote myocardial microvascular function and architecture, despite enduring hypertension. These findings underscore functionally important cardiorenal crosstalk possibly mediated by renal injury signals.
|Original language||English (US)|
|Number of pages||9|
|State||Published - Apr 2012|
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine