Effects of heparin and derivatives on podocytes: An in vitro functional and morphological evaluation

Abstract

Unfractionated heparin (UFH) and low molecular heparin derivatives (LMWH) display numerous biological properties in addition to their anticoagulant effects. However, due to the physicochemical heterogeneity of these drugs, a better understanding concerning their effects on human cells is clearly needed. Considering that heparins are mainly excreted by the kidney, we focused our attention on the effect of UFH and LMWH on human podocytes by functional and morphological/phenotypic in vitro analyses. We demonstrated that these products differentially modulate the permeability of podocyte monolayer to albumin. The functional perturbations observed were correlated to significant cellular morphological and cytoskeletal changes, as well as a decrease in the expression of proteins involved in podocyte adherence to the extracellular matrix or intercellular interactions. This point confirms that UFH and the different LMWHs exert specific effects on podocyte permeability and underlines the need of in vitro tests to evaluate new biological nonanticoagulant properties of LMWH.

Low molecular weight heparin (nadroparin) improves placental permeability in rats with gestational diabetes mellitus via reduction of tight junction factors

“…Yalniz et al (44) reported that nadroparin exerts anti-oxidative and anti-inflammatory effects by regulating the nF-κB and nuclear factor erythroid 2-related factor 2/heme oxygenase 1 pathways. in contrast to tinzaparin, fondaparinux or to direct oral anticoagulants, enoxaparin increases the permeability of podocytes to albumin, as reported by delézay et al (45). The heterogeneity of lMWHs may explain these inconsistent and even opposite conclusions.…”

Non-reducing End of Heparin Tri-saccharide is a Scavenger Tool to Detoxify the Glucose Toxicity in Diabetes

“…However, the mechanism(s) are still unclear. Particularly pertinent to our studies, a recent study concluded that unfractionated heparin (UFH) and the different low MW heparins (LMWHs) exert specific effects on podocyte permeability, and they underline the need of in vivo tests to evaluate new biological non-anticoagulant properties of LMWH [ 36 ]. Thus, a future study is needed to determine the roles of heparin/Hep-Tri in detoxifying the glucose toxicity resulting from hyperglycemia.…”

“…LMWH [36]. Thus, a future study is needed to determine the roles of heparin/Hep-Tri in detoxifying the glucose toxicity resulting from hyperglycemia.…”