Improving Treatment in Atherosclerotic Renal Artery Stenosis (ARAS)
Renal artery stenosis (RAS), which is most commonly caused by atherosclerosis, has an incidence rate of almost 7% in the older adult population.
Patients with atherosclerotic renal artery stenosis (ARAS), also called renovascular disease (RVD), have increased risk of developing cardiovascular disease and progression to end-stage renal failure.
A common intervention in patients with atherosclerotic renal artery stenosis is the restoration of vessel patency by revascularization. But the procedure's ability to restore renal function and improve blood pressure control is still controversial.
Therefore, strategies to more effectively preserve kidney function distal to the stenosis are urgently needed.
Our research team has been engaged in elucidating mechanisms of renal injury in ARAS for the past two decades. Our recent focus has been on different strategies to improve the response to revascularization.
We also recently developed and characterized a novel swine model of ARAS and unique physiological imaging techniques that allow study of the single-kidney function and structure, both in vivo and in vitro. Even more recently, our team has explored the effect of metabolic syndrome on renal injury in renal artery stenosis.
Our studies related to improving treatment in atherosclerotic renal artery stenosis include:
- Cell-based therapy, including stem and stromal cells; stem cell derivatives, such as extracellular vesicles; and resident stem and progenitor cells
- Mitochondria-targeted drugs
- Growth factors
- Senolytic drugs
- Low-energy ultrasound shock wave therapy
Stem cell therapy
Therapeutic utilization of progenitor cells and stem cells is becoming an attractive alternative to conventional treatments, especially for diseases that are refractory to other treatments.
Recent projects involved delivery of adipose tissue-derived mesenchymal stem cells (MSC) into the stenotic kidney with or without concurrent revascularization to restore cellular integrity and to decrease the progression to renal failure in swine models and in patients with ARAS.
Our current projects involve delivery of mesenchymal stem cells in metabolic syndrome and characterization and delivery of MSC-derived membrane microparticles (extracellular vesicles, such as microvesicles and exosomes) using RNA-seq, proteomics and epigenetic approaches.
One of the potential underlying causes for the failure of revascularization to restore renal function is mitochondrial damage. MTP-131 (bendavia) is a novel compound that targets the mitochondria to stabilize cardiolipin, improve energy utilization and attenuate apoptosis associated with cardiovascular insults.
Our research evaluates the potential effects of intrarenal infusion or subcutaneous injections of bendavia for improving renal function and reducing apoptosis and the progression to fibrosis in the swine ARAS kidney and heart and in metabolic syndrome.
Cellular senescence is a cellular program characterized by a permanent cell-cycle arrest that eventually alters cell function. Cellular senescence leads cells to acquire a senescence-associated secretory phenotype (SASP), a secretome comprised of cytokines, chemokines and growth factors. Aberrant and chronic accumulation of senescent cells harboring the SASP phenotype can exert noxious effects on neighboring cells and drive feed-forward premature aging and tissue injury.
Senolytic compounds target pro-survival pathways in senescent cells, and thereby facilitate their elimination.
Our research evaluates the role of cellular senescence in driving renal and cardiac injury and the potential beneficial effects of senolytic drugs.
For more information about our project on improving treatment in atherosclerotic renal artery stenosis, email Alfonso Eirin Massat, M.D.