Dr. Taya Bezhaeva

Postdoc

Research

“Currently, I am focusing on therapeutic strategies to induce new capillary formation (angiogenesis) and improve the overall quality of the microvasculature in the myocardium. In particular, I study endothelial (dys)function, capillary maturation and leakiness, and vasoconstriction/vasodilation.

For evaluation of therapeutic approaches aiming to maintain or increase cardiac function of the (explanted) heart I use a number of in vivo and in vitro models including myocardial infarction and ex vivo cultured mouse hearts. In my work I apply state-of-the-art imaging techniques such as VEVO-LAZRx photoacoustic imaging, two-photon and light-sheet microscopy to study the therapeutic effects on vascular integrity in 3D.”

Several research lines include:

The role of dietary restriction, specifically H2S.H2Sn and its prodrugs for beneficial tissue survival
The role of relaxin as a potential target to improve cardiac function
Role of 14Q32 microRNAs in angiogenesis, endothelial function and capillary maturation
Role of VEGF and related factors
The role of maturation increasing factors in preservation of the myocardium

Curriculum Vitae

“I am a dedicated scientist backed by more than 10 years of international research experience in both academic and industrial sectors.

I did my PhD at the Leiden University Medical Centre (LUMC) department of vascular and regenerative medicine, where I was unravelling haemodialysis vascular access failure – a major vascular complication in patients with end-stage renal disease. Obtaining a grant from the Dutch Kidney Foundation facilitated me to join the department of biomedical engineering at the University California, Los Angeles. Here, I was working on in situ engineered replacement of damaged vessels.

After obtaining my PhD, I continued to work as a Postdoctoral Fellow in a consortium between Leiden University and the University of Amsterdam. Under the supervision of dr. Rotmans and prof. Nieuwdorp I was studying the role of gut-microbiome-kidney axis in the progression of diabetic nephropathy.

Driven by my interest in data science and analytics over a short period I joined the life science consultancy team at Elsevier. Sharing expertise in several scientific domains I was in volved in big data harmonization, aiming to accelerate drug discoveries, and identify potential drug and patient safety signals for a number of pharma and academic customers.

Now I work within the RegMed XB consortia that comprises a public-private partnership between governments, health foundations, academic and industrial companies. At the LUMC I work in the vascular surgery group headed by Prof. Quax. We actively collaborate with prof. Goumans at the department of Cell and Chemical Biology, and dr. de Vries at the department of experimental Cardiology.”

Recent publications

The pathophysiology of arteriovenous fistula (AVF) maturation failure is not completely understood but impaired outward remodeling (OR) and intimal hyperplasia are thought to be contributors. This adverse vascular response after AVF surgery results from interplay between vascular smooth muscle cells (VSMCs), the extracellular matrix (ECM), and inflammatory cells. Relaxin (RLN) is a hormone that acts on the vasculature via interaction with RLN/insulin-like peptide family receptor 1 (RXFP1), resulting in vasodilatation, ECM remodeling, and decreased inflammation. In the present study, we evaluated the consequences of RXFP1 knockout ( Rxfp1) on AVF maturation in a murine model of AVF failure. Rxfp1 mice showed a 22% decrease in vessel size at the venous outflow tract 14 d after AVF surgery. Furthermore, a 43% increase in elastin content was observed in the lesions of Rxfp1 mice and coincided with a 41% reduction in elastase activity. In addition, Rxfp1 mice displayed a 6-fold increase in CD45 leukocytes, along with a 2-fold increase in monocyte chemoattractant protein 1 (MCP1) levels, when compared with wild-type mice. In vitro, VSMCs from Rxfp1 mice exhibited a synthetic phenotype, as illustrated by augmentation of collagen, fibronectin, TGF-β, and platelet-derived growth factor mRNA. In addition, VSMCs derived from Rxfp1 mice showed a 5-fold increase in cell migration. Finally, RXFP1 and RLN expression levels were increased in human AVFs when compared with unoperated cephalic veins. In conclusion, RXFP1 deficiency hampers elastin degradation and results in induced vascular inflammation after AVF surgery. These processes impair OR in murine AVF, suggesting that the RLN axis could be a potential therapeutic target for promoting AVF maturation.-Bezhaeva, T., de Vries, M. R., Geelhoed, W. J., van der Veer, E. P., Versteeg, S., van Alem, C. M. A., Voorzaat, B. M., Eijkelkamp, N., van der Bogt, K. E., Agoulnik, A. I., van Zonneveld, A.-J., Quax, P. H. A., Rotmans, J. I. Relaxin receptor deficiency promotes vascular inflammation and impairs outward remodeling in arteriovenous fistulas.

Activation of Toll like receptors (TLR) plays an important role in cardiovascular disease development, progression and outcomes. Complex TLR mediated signaling affects vascular and cardiac function including tissue remodeling and repair. Being central components of both innate and adaptive arms of the immune system, TLRs interact as pattern recognition receptors with a series of exogenous ligands and endogenous molecules or so-called danger associated molecular patterns (DAMPs) that are released upon tissue injury and cellular stress. Besides immune cells, a number of structural cells within the cardiovascular system, including endothelial cells, smooth muscle cells, fibroblasts and cardiac myocytes express TLRs and are able to release or sense DAMPs. Local activation of TLR-mediated signaling cascade induces cardiovascular tissue repair but in a presence of constant stimuli can overshoot and cause chronic inflammation and tissue damage. TLR accessory molecules are essential in guiding and dampening these responses toward an adequate reaction. Furthermore, accessory molecules assure specific and exclusive TLR-mediated signal transduction for distinct cells and pathways involved in the pathogenesis of cardiovascular diseases. Although much has been learned about TLRs activation in cardiovascular remodeling, the exact role of TLR accessory molecules is not entirely understood. Deeper understanding of the role of TLR accessory molecules in cardiovascular system may open therapeutic avenues aiming at manipulation of inflammatory response in cardiovascular disease. The present review outlines accessory molecules for membrane TLRs that are involved in cardiovascular disease progression. We first summarize the up-to-date knowledge on TLR signaling focusing on membrane TLRs and their ligands that play a key role in cardiovascular system. We then survey the current evidence of the contribution of TLRs accessory molecules in vascular and cardiac remodeling including myocardial infarction, heart failure, stroke, atherosclerosis, vein graft disease and arterio-venous fistula failure.