Abstract
IntroductionPercutaneous transluminal renal angioplasty (PTRA) fails to fully improve cardiac injury and dysfunction in patients with renovascular hypertension (RVH). Mesenchymal stem cells (MSCs) restore renal function, but their potential for attenuating cardiac injury after reversal of RVH has not been explored. We hypothesized that replenishment of MSCs during PTRA would improve cardiac function and oxygenation, and decrease myocardial injury in porcine RVH.MethodsPigs were studied after 16 weeks of RVH, RVH treated 4 weeks earlier with PTRA with or without adjunct intra-renal delivery of MSC (10^6 cells), and controls. Cardiac structure, function (fast-computed tomography (CT)), and myocardial oxygenation (Blood-Oxygen-Level-Dependent- magnetic resonance imaging) were assessed in-vivo. Myocardial microvascular density (micro-CT) and myocardial injury were evaluated ex-vivo. Kidney venous and systemic blood levels of inflammatory markers were measured and their renal release calculated.ResultsPTRA normalized blood pressure, yet stenotic-kidney glomerular filtration rate, similarly blunted in RVH and RVH + PTRA, normalized only in PTRA + MSC-treated pigs. PTRA attenuated left ventricular remodeling, whereas myocardial oxygenation, subendocardial microvascular density, and diastolic function remained decreased in RVH + PTRA, but normalized in RVH + PTRA-MSC. Circulating isoprostane levels and renal release of inflammatory cytokines increased in RVH and RVH + PTRA, but normalized in RVH + PTRA-MSC, as did myocardial oxidative stress, inflammation, collagen deposition, and fibrosis.ConclusionsIntra-renal MSC delivery during PTRA preserved stenotic-kidney function, reduced systemic oxidative stress and inflammation, and thereby improved cardiac function, oxygenation, and myocardial injury four weeks after revascularization, suggesting a therapeutic potential for adjunctive MSC delivery to preserve cardiac function and structure after reversal of experimental RVH.
Highlights
Percutaneous transluminal renal angioplasty (PTRA) fails to fully improve cardiac injury and dysfunction in patients with renovascular hypertension (RVH)
Four weeks after successful PTRA (0% stenosis in all PTRA-treated pigs), mean arterial pressure (MAP) normalized in RVH + PTRA and RVH + PTRA + Mesenchymal stem cells (MSC) pigs (Table 1, Figure 1A-B)
Total cholesterol and low-density lipoprotein (LDL) levels were elevated in all RVH groups compared to normal, whereas high-density lipoprotein (HDL) and triglyceride levels did not differ among the groups (Table 1)
Summary
Percutaneous transluminal renal angioplasty (PTRA) fails to fully improve cardiac injury and dysfunction in patients with renovascular hypertension (RVH). We hypothesized that replenishment of MSCs during PTRA would improve cardiac function and oxygenation, and decrease myocardial injury in porcine RVH. Among hypertensive patients undergoing echocardiography, cardiac structure and diastolic function are more compromised in RVH than in essential hypertensive patients, and its Restoring blood flow to the kidney by percutaneous transluminal renal angioplasty (PTRA) has become a common approach among interventional cardiologists and radiologists [3]. Despite successful restoration of vessel patency with PTRA, inflammatory cytokines and oxidative stress markers remain elevated and glomerular filtration rate (GFR) fails to recover in both porcine and human RVH [10,11], underscoring the need for strategies tailored to ameliorate inflammation and oxidative stress
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