Intrarenal modulation of NF-κB activity attenuates cardiac injury in a swine model of CKD: a renal-cardio axis.

Patients with chronic kidney disease (CKD) have a high cardiovascular mortality. CKD and heart failure (HF) coexist in up to 50% of patients, and both associate with inflammation. We aimed to define the cardiac phenotype of a novel swine model of CKD and test the hypothesis that inflammation of renal origin propels the development of precursors of HF in CKD.

Recovery of Renal Function following Kidney-Specific VEGF Therapy in Experimental Renovascular Disease.

Background: Chronic renovascular disease (RVD) can lead to a progressive loss of renal function, and current treatments are inefficient. We designed a fusion of vascular endothelial growth factor (VEGF) conjugated to an elastin-like polypeptide (ELP) carrier protein with an N-terminal kidney-targeting peptide (KTP). We tested the hypothesis that KTP-ELP-VEGF therapy will effectively recover renal function with an improved targeting profile.

Molecular targeting of renal inflammation using drug delivery technology to inhibit NF-κB improves renal recovery in chronic kidney disease.

Inflammation is a major determinant for the progression of chronic kidney disease (CKD). NF-κB is a master transcription factor upregulated in CKD that promotes inflammation and regulates apoptosis and vascular remodeling. We aimed to modulate this pathway for CKD therapy in a swine model of CKD using a peptide inhibitor of the NF-κB p50 subunit (p50i) fused to a protein carrier [elastin-like polypeptide (ELP)] and equipped with a cell-penetrating peptide (SynB1).

Macrophage polarization in chronic kidney disease: a balancing act between renal recovery and decline?

Macrophages are heterogenous cells of the innate immune system that can fluidly modulate their phenotype to respond to their local microenvironment. They are found throughout the renal compartments, where they contribute to homeostasis and function. However, renal injury activates molecular pathways that initially stimulate differentiation of macrophages into a proinflammatory M1 phenotype.

Targeted VEGF (Vascular Endothelial Growth Factor) Therapy Induces Long-Term Renal Recovery in Chronic Kidney Disease via Macrophage Polarization.

Chronic kidney disease (CKD) universally associates with renal microvascular rarefaction and inflammation, but whether a link exists between these 2 processes is unclear. We designed a therapeutic construct of VEGF (vascular endothelial growth factor) fused to an ELP (elastin-like polypeptide) carrier and show that it improves renal function in experimental renovascular disease. We test the hypothesis that ELP-VEGF therapy will improve CKD, and that recovery will be driven by decreasing microvascular rarefaction partly via modulation of macrophage phenotype and inflammation.

Biopolymer-delivered vascular endothelial growth factor improves renal outcomes following revascularization.

Renal angioplasty and stenting (PTRAs) resolves renal artery stenosis, but inconsistently improves renal function, possibly due to persistent parenchymal damage. We developed a bioengineered fusion of a drug delivery vector (elastin-like polypeptide, ELP) with vascular endothelial growth factor (VEGF), and showed its therapeutic efficacy. We tested the hypothesis that combined ELP-VEGF therapy with PTRAs improves renal recovery more efficiently than PTRAs alone, by protecting the stenotic renal parenchyma.

Vascular Endothelial Growth Factor and Podocyte Protection in Chronic Hypoxia: Effects of Endothelin-A Receptor Antagonism.

Background: Podocytes are major components of the filtration barrier and a renal source of vascular endothelial growth factor (VEGF). Chronic renovascular disease (RVD) progressively degrades the renal function, accompanied by podocyte damage and a progressive reduction in VEGF. We showed that the endothelin (ET) pathway contributes to this pathological process and ET-A (but not ET-B) receptor antagonism protects the kidney in RVD.