TY - JOUR
T1 - Selective improvement in renal function preserved remote myocardial microvascular integrity and architecture in experimental renovascular disease
AU - Urbieta-Caceres, Victor H.
AU - Zhu, Xiang Yang
AU - Jordan, Kyra L.
AU - Tang, Hui
AU - Textor, Kyle
AU - Lerman, Amir
AU - Lerman, Lilach O.
N1 - Funding Information:
This study was partly supported by grant numbers DK-73608 , DK77013 , HL-77131 , PO1HL-085307 , and RR018898 from the NIH .
PY - 2012/4
Y1 - 2012/4
N2 - 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.
AB - 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.
KW - Atherosclerosis
KW - Inflammation
KW - Microcirculation
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U2 - 10.1016/j.atherosclerosis.2011.10.005
DO - 10.1016/j.atherosclerosis.2011.10.005
M3 - Article
C2 - 22341593
AN - SCOPUS:84862793020
SN - 0021-9150
VL - 221
SP - 350
EP - 358
JO - Atherosclerosis
JF - Atherosclerosis
IS - 2
ER -