Selective improvement in renal function preserved remote myocardial microvascular integrity and architecture in experimental renovascular disease

Victor H. Urbieta-Caceres, Xiang Yang Zhu, Kyra L. Jordan, Hui Tang, Kyle Textor, Amir Lerman, Lilach O Lerman

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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 languageEnglish (US)
Pages (from-to)350-358
Number of pages9
JournalAtherosclerosis
Volume221
Issue number2
DOIs
StatePublished - Apr 2012

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Kidney
Oxidative Stress
Renal Veins
Capillary Permeability
Transforming Growth Factors
Inflammation
Aldosterone
Adenosine
Swine
Isoprostanes
Renovascular Hypertension
Hypercholesterolemia
Uric Acid
Glomerular Filtration Rate
Cardiomyopathies
Fibrosis
Cardiovascular Diseases
Blood Pressure
Hypertension
Morbidity

Keywords

  • Atherosclerosis
  • Inflammation
  • Microcirculation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Selective improvement in renal function preserved remote myocardial microvascular integrity and architecture in experimental renovascular disease. / Urbieta-Caceres, Victor H.; Zhu, Xiang Yang; Jordan, Kyra L.; Tang, Hui; Textor, Kyle; Lerman, Amir; Lerman, Lilach O.

In: Atherosclerosis, Vol. 221, No. 2, 04.2012, p. 350-358.

Research output: Contribution to journalArticle

Urbieta-Caceres, Victor H. ; Zhu, Xiang Yang ; Jordan, Kyra L. ; Tang, Hui ; Textor, Kyle ; Lerman, Amir ; Lerman, Lilach O. / Selective improvement in renal function preserved remote myocardial microvascular integrity and architecture in experimental renovascular disease. In: Atherosclerosis. 2012 ; Vol. 221, No. 2. pp. 350-358.
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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.

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