Different apoptotic responses of human and bovine pericytes to fluctuating glucose levels and protective role of thiamine

Abstract

Human pericytes are less prone to apoptosis induced by persistently high glucose than bovine cells. However, while BRP recover after returning to physiological levels, HRP are more vulnerable to both downwardly fluctuating glucose levels and intermittent exposure. These findings reinforce the hypotheses that (1) glycaemic fluctuations play a role in the development of diabetic retinopathy and (2) species-specific models are needed. Thiamine and benfotiamine prevent human pericyte apoptosis, indicating this vitamin as an inexpensive approach to the prevention and/or treatment of diabetic complications.

Human pericyte–endothelial cell interactions in co-culture models mimicking the diabetic retinal microvascular environment

“…In our models, both cell types reduced their proliferation and increased apoptosis when co-cultured in stable high glucose conditions. This happened also in EC cultured alone, consistently with previous evidence in the literature [23][24][25], while HRP in solo cultures showed neither reduced proliferation nor increased apoptosis, confirming our previous data on low sensitivity of human pericytes to persistently high glucose in comparison with bovine cells [5]. Exposure to intermittent high glucose in the contact model, on the contrary, resulted in decreased proliferation and increased apoptosis in all cases, including HRP alone, consistently with our previous findings that HRP are vulnerable to both downwardly fluctuating glucose levels and intermittent exposure [5].…”

“…High glucose concentrations reduced proliferation (both counts and DNA synthesis) and enhanced apoptosis in EC and HRP in co-cultures, and in EC alone, while it had no effect when HRP were cultured alone, similarly to our previous observations [5] demonstrating that human pericytes alone are not affected by stable high glucose conditions.…”

“…We have demonstrated great differences between bovine and human retinal pericytes cultured in diabetic-like conditions: human pericytes are less sensitive to apoptosis induced by steadily high glucose than BRP, but are vulnerable to intermittent exposure to high and physiological glucose [5] and to culture on ECM produced by EC cultured in high glucose conditions [6]. For this reason, an immortalized human retinal pericyte line, with extended proliferation capability and stable differentiation, together with an ability to be influenced by glucose toxicity completely super-imposable to the one of the primary cells from which it was derived [5], was established and characterized in our lab [3] and used for this study.…”

“…The human retinal pericyte line (HRP) established in our laboratory [3] allows to obtain species-specific data. In fact, observations from our and other laboratories [4][5][6] suggest that human and bovine retinal pericytes (BRP) behave differently in experimental conditions designed to mimic the diabetic milieu. HRP are less prone to apoptosis induced by persistently high glucose than BRP.…”

“…HRP are less prone to apoptosis induced by persistently high glucose than BRP. However, while BRP recover after returning to physiological levels, human pericytes are more vulnerable to both downwardly fluctuating glucose levels and intermittent exposure [5]. Apoptosis is strongly increased in HRP, but not in BRP, when they are cultured on extracellular matrix (ECM) produced by endothelium in high glucose conditions [6].…”