Vascular growth factors as potential new treatment in cardiorenal syndrome in diabetes

Ricciardi, Carlo Alberto; Gnudi, Luigi

doi:10.1111/eci.13579

Cited by 9 publications

(6 citation statements)

References 99 publications

(132 reference statements)

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“…It has been reported that diminished endothelial density is a common phenomenon in the kidney of I/R-induced AKI ( Wu et al, 2021 ), whereas increased expression of VEGFA and in its receptor VEGFR2 is associated with renal neovascularization ( Ricciardi and Gnudi, 2021 ). To further explore whether MSCs-derived exosomes would protect against AKI via regulating renal angiogenesis in the pig model of AKI, we examined the effect of exosomes on the expression of VEGFA and VEGFR2 in the kidney.…”

Section: Resultsmentioning

confidence: 99%

Mesenchymal Stem Cells-Derived Exosomes Ameliorate Ischemia/Reperfusion Induced Acute Kidney Injury in a Porcine Model

Huang

Cao

Cui

et al. 2022

Front. Cell Dev. Biol.

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Exosomes are membrane-enclosed vesicles secreted by cells, containing a variety of biologically active ingredients including proteins, nucleic acids and lipids. In this study, we investigated the therapeutic effects of the exosomes and underlying mechanisms in a miniature pig model of ischemia/reperfusion-induced acute kidney injury (I/R-AKI). The exosomes were extracted from cultured human umbilical cord derived mesenchymal stem cells (hUC-MSCs) and infused into a miniature pig model of I/R AKI. Our results showed that 120 min of unilateral ischemia followed by reperfusion and contralateral nephrectomy resulted in renal dysfunction, severe kidney damage, apoptosis and necroptosis. Intravenous infusion of one dose of exosomes collected from about 4 × 108 hUC-MSCs significantly improved renal function and reduced apoptosis and necroptosis. Administration of hUC-MSC exosomes also reduced the expression of some pro-inflammatory cytokines/chemokines, decreased infiltration of macrophages to the injured kidneys and suppressed the phosphorylation of nuclear factor-κB and signal transducer and activator of transcription 3, two transcriptional factors related to inflammatory regulation. Moreover, hUC-MSC exosomes could promote proliferation of renal tubular cells, angiogenesis and upregulation of Klotho and Bone Morphogenetic Protein 7, two renoprotective molecules and vascular endothelial growth factor A and its receptor. Collectively, our results suggest that injection of hUC-MSC exosomes could ameliorate I/R-AKI and accelerate renal tubular cell repair and regeneration, and that hUC-MSC exosomes may be used as a potential biological therapy for Acute kidney injury patients.

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Section: Resultsmentioning

confidence: 99%

Mesenchymal Stem Cells-Derived Exosomes Ameliorate Ischemia/Reperfusion Induced Acute Kidney Injury in a Porcine Model

Huang

Cao

Cui

et al. 2022

Front. Cell Dev. Biol.

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“…An independent role of Angpt2 in predicting adverse cardiorenal outcomes in patient with diabetes, coronary artery disease and HF has been described [ 46 ]. An increased Angpt2/Angpt1 ratio in the myocardium favors endothelium apoptosis and inflammation, which have been associated with the severity of renal impairment and albuminuria [ 47 ].…”

Section: Pathophysiology Of Cardiorenal Syndromementioning

confidence: 99%

New Insight in Cardiorenal Syndrome: From Biomarkers to Therapy

Gallo

Lanza

Savoia

2023

IJMS

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Cardiorenal syndrome consists in the coexistence of acute or chronic dysfunction of heart and kidneys resulting in a cascade of feedback mechanisms and causing damage to both organs associated with high morbidity and mortality. In the last few years, different biomarkers have been investigated with the aim to achieve an early and accurate diagnosis of cardiorenal syndrome, to provide a prognostic role and to guide the development of targeted pharmacological and non-pharmacological therapies. In such a context, sodium-glucose cotransporter 2 (SGLT2) inhibitors, recommended as the first-line choice in the management of heart failure, might represent a promising strategy in the management of cardiorenal syndrome due to their efficacy in reducing both cardiac and renal outcomes. In this review, we will discuss the current knowledge on the pathophysiology of cardiorenal syndrome in adults, as well as the utility of biomarkers in cardiac and kidney dysfunction and potential insights into novel therapeutics.

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“…Inhibition of the increased VEGFA production in DN have so far been frustrating, with severe adverse effects [ 59 ] including glomerular thrombotic microangiopathy [ 60 , 61 ]. However potential new approaches may be feasible [ 62 ]. Recent experimental studies [ 63 ] have described a reduction of podocytic VEGF by SLGT2 inhibition.…”

Section: Histopathology and Therapeutic Optionsmentioning

confidence: 99%

The complex pathology of diabetic nephropathy in humans

Kriz

Löwen

Gröne

2023

Nephrology Dialysis Transplantation

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This review summarizes the pathomorphological sequences of nephron loss in human diabetic nephropathy (DN). The relevant changes may be derived from two major derangements. First, a failure in the turnover of the glomerular basement membrane (GBM) based on an increased production of GBM components by podocytes and endothelial cells leading to the thickening of the GBM and accumulation of worn-out GBM in the mesangium. This failure may account for the direct pathway to glomerular compaction and sclerosis based on the continuous deposition of undegraded GBM-material in the mesangium. Second, an increased leakiness together with an increased propensity of glomerular capillaries to proliferate leads to widespread plasma exudations. Detrimental are those that produce giant insudative spaces within Bowman's capsule (BC) spreading around the entire glomerular circumference and along the glomerulo-tubular junction onto the tubule resulting in tubular obstruction and retroactively to glomerulosclerosis. Tubular atrophy and interstitial fibrosis develop secondarily by transfer of the glomerular damage onto the tubule. Interstitial fibrosis is locally initiated and apparently stimulated by degenerating tubular epithelia. This leads to a focal distribution of interstitial fibrosis and tubular atrophy (IFTA) accompanied by a varying interstitial mononuclear cell infiltration. Spreading of fibrotic areas between intact nephrons, much less to the glomerulus, has not been encountered.

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Vascular growth factors as potential new treatment in cardiorenal syndrome in diabetes

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 9 publications

References 99 publications

Mesenchymal Stem Cells-Derived Exosomes Ameliorate Ischemia/Reperfusion Induced Acute Kidney Injury in a Porcine Model

Mesenchymal Stem Cells-Derived Exosomes Ameliorate Ischemia/Reperfusion Induced Acute Kidney Injury in a Porcine Model

New Insight in Cardiorenal Syndrome: From Biomarkers to Therapy

The complex pathology of diabetic nephropathy in humans

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