Our research focuses on impaired microvascular functions in obesity and type 2 diabetes, which contribute to organ failure in these conditions. The hallmark of which is impairment of organ blood flow, which occurs early in the pathogenesis of type diabetes and is detectable before symptoms of disease. Microvascular dysfunction and impaired organ blood flow result from complex interactions between fat tissue, the kidneys and the immune system.
The microcirculation of different organs has different functions, including regulation of local blood flow, inflammation and metabolism. In turn these microvascular functions control organ function and dysfunction, including heart failure, myocardial ischemia and cognitive decline. Diabetes, hypertension and obesity, known as the metabolic syndrome in combination with dyslipidemia, are chronic conditions associated with impaired organ blood flow and inflammation. Microvascular dysfunction in the metabolic syndrome is characterized by increased arteriolar resistance, reduced capillary density and blood flow and an imbalance between endothelial secretion of vasodilator and vasoconstrictor substances. A type of microvascular dysfunction specific to the metabolic syndrome is impairment of insulin-induced vasodilation. While well-known in organ physiology and modeling of organ failure, microvascular function in the clinic is mostly used to model human disease and has not fully implemented in diagnosis or therapy.
We have shown that fat tissue around blood vessels, or perivascular adipose tissue (PVAT) in regulation of normal and impaired organ blood flow. For instance, reduced muscle perfusion contributes to insulin resistance and reduced exercise capacity in obesity and type 2 diabetes, while microvascular inflammation and reduced perfusion impair myocardial function. This research started with our hypothesis paper published in the leading medical journal The Lancet and has resulted in evidence that PVAT controls muscle blood flow through a balance of vasodilator and vasoconstrictor products, known as adipokines. While the balance between these two is tilted towards vasodilator adipokines in normal physiology, it shifts towards vasoconstrictor adipokines in obesity, even in before diseases such as type 2 diabetes occur. We have also shown that kidney failure, a complication of obesity and diabetes, has a separate and aggravating effect on organ blood flow through reduction of the synthesis of nitric oxide.
As we study interactions between fat tissue function, organ blood flow and glucose metabolism, we have expertise in analysis and manipulation of these characteristics. Specific techniques used in our group:
Netherlands Heart Foundation, consortium grant (CVON Reconnect)
Netherlands Heart Foundation, innovation grant
Netherlands Heart Institute, project grant
European Union, European Training Network grant (IMPROVE-PD)
Netherlands Organisation for Scientific Research (NWO), Vidi grant
Danish research foundation
Netherlands Kidney Foundation (consortium grant)
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6. Meijer RI, Hoevenaars FPM, Serne EH, Yudkin JS, Kokhuis TJA, Weijers EM, van Hinsbergh VWM, Smulders YM and Eringa EC. JNK2 in myeloid cells impairs insulin's vasodilator effects in muscle during early obesity development through perivascular adipose tissue dysfunction. Am J Physiol Heart Circ Physiol. 2019;317:H364-h374.
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8. Turaihi AH, Bakker W, van Hinsbergh VWM, Serné EH, Smulders YM, Niessen HWM and Eringa EC. Insulin Receptor Substrate 2 Controls Insulin-Mediated Vasoreactivity and Perivascular Adipose Tissue Function in Muscle. Front Physiol. 2018;9:245.
9. Verkaik M, Oranje M, Abdurrachim D, Goebel M, Gam Z, Prompers JJ, Helmes M, Ter Wee PM, van der Velden J, Kuster DW, Vervloet MG and Eringa EC. High Fibroblast Growth Factor 23 concentrations in experimental renal failure impair calcium handling in cardiomyocytes. Physiological reports. 2018;6:e13591.
10. Verkaik M, Juni RP, van Loon EPM, van Poelgeest EM, Kwekkeboom RFJ, Gam Z, Richards WG, Ter Wee PM, Hoenderop JG, Eringa EC and Vervloet MG. FGF23 impairs peripheral microvascular function in renal failure. Am J Physiol Heart Circ Physiol. 2018;315:H1414-h1424.
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