Vascular Kinetics Laboratory Overview

Endothelial cells regulate vascular homeostasis from their unique position at the blood-tissue interface. In this complex environment, endothelial cells dynamically integrate biochemical and mechanical stimulation from the flowing blood at their apical surface and the vascular wall at their basolateral surface. Disturbances in the biochemical and biomechanical environment, such as elevated glucose or low shear stress, can lead to endothelial dysfunction and subsequent cardiovascular disease.

The Vascular Kinetics Laboratory conducts research at the interface of engineering, biochemistry, and vascular biology. In our prior work, we largely focused on how an altered glucose environment (e.g., in diabetes) impaired endothelial cell response to shear stress and cyclic strain. We demonstrated that endothelial cells in high glucose do not respond appropriately to mechanical stimuli. Today, we focus primarily on the opposite question- how the mechanical environment affects endothelial cell glucose metabolism. We are integrating mechanobiology and metabolism, with the hope of using metabolic engineering to decrease the burden of cardiovascular disease and cancer. With new collaboration opportunities at the University of Maryland, we plan to extend our cell and animal work into human studies.

Research Projects

Laminar and Disturbed Flow Effects on Endothelial Glucose Metabolism

Endothelial metabolism has recently emerged as a powerful tool to regulate the abnormal microvasculature in cancer. When glycolysis is blocked, endothelial cells are no longer able to form new blood vessels in vitro or in vivo. However, little is known about how endothelial cell metabolism impacts macrovascular endothelial function in health and disease. When arterial endothelial cells adapt to steady laminar flow, they express a quiescent phenotype, maintaining vascular homeostasis through tight control of proliferation, permeability, inflammation, and vascular tone. When endothelial cells fail to adapt to flow, for example in areas of oscillating disturbed flow, they maintain a round morphology with elevated proliferation, permeability, and inflammatory adhesion molecule expression as well as impaired nitric oxide (NO) production (collectively defined as endothelial dysfunction). These disturbed flow regions are linked to subsequent vascular pathology, including atherosclerotic plaque development. Our goal is to understand how vascular hemodynamics regulates endothelial glucose metabolism, and how endothelial glucose metabolism can be modulated to reduce endothelial dysfunction in disturbed flow. Our data show that endothelial cells decrease glycolytic flux in steady laminar but not oscillating disturbed flow. Our data also show that steady laminar and oscillating disturbed flow differentially regulate side branches of glycolysis including the hexosamine biosynthetic pathway, which controls the post-translational protein modification O-GlcNAcylation. The goal of this project is to understand how steady laminar and oscillating disturbed flow differentially affect macrovascular endothelial glycolytic flux. We further aim to determine how these metabolic pathways impact endothelial dysfunction in vitro and ex vivo.


Steady Laminar

Oscillating Disturbed




p - eNOS



Computational Models of Endothelial Glucose Metabolism

Cellular metabolism is a complex, branched, recursive network with many interlinked pathways through which multiple metabolites are used to create energy for the cell as well as a multitude of other purposes (e.g., amino acid synthesis, post-translational protein modifications, oxidative stress reduction). While some groups have postulated that blocking one metabolic pathway (e.g., glycolysis) will inhibit a specific cell function (e.g., angiogenesis), we believe that we must first understand the system-level effects of metabolic inhibitors on the entire metabolic network to effectively create metabolic therapies. We are therefore using a combination of experimental and computational techniques to understand how metabolism is perturbed under different conditions. In order to quantify alterations in metabolic flux from experimental samples, we are utilizing a technique known as metabolic flux analysis. By incorporating measured extracellular fluxes, metabolite isotopomer distributions, and simplified metabolic maps in computational models, we can infer the metabolic fluxes of our experimental samples.  These results can be further extended to develop predictive metabolic models. By utilizing RECON3D, together with endothelial gene expression data sets and inferred fluxomic distributions, we are developing a computational model of endothelial cell metabolism that can predict how metabolism is altered under conditions such as substrate depletion or pharmacological treatment. In the future, we hope to expand this computational model to better understand how endothelial cells use and transport metabolites in concert with surrounding parenchymal cells, for example to better understand changes in glucose metabolism in diseases such as cancer and Alzheimer’s.

Impaired endothelial mechanosensing in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a progressive, fatal disease in which decreased pulmonary vascular lumen leads to increased pulmonary resistance and eventual right heart failure. The decrease in vascular lumen relates to imbalances in vascular tone and cell proliferation. Endothelial cells in particular have been shown to metabolize more glucose and produce less nitric oxide (NO) in PAH, both of which may contribute to disease pathology. Our goal is to elucidate the mechanical and metabolic pathways underlying endothelial dysfunction in PAH to identify new treatments for this incurable disease. Our data show that human pulmonary artery endothelial cells from patients with PAH are metabolically distinct from normal human pulmonary artery cells, and the PAH cells may adapt differently to fluid flow. We will determine how flow affects glucose metabolism in normal and PAH human endothelial cells in vitro and how restoring the effects of flow stimulation impacts pulmonary artery structure and pressure in a mouse model of bronchopulmonary dysplasia in vivo.






Arterial stiffness in spinal cord injury

Cardiovascular disease is the leading cause of death in the chronically spinal cord injured (SCI) population. Individuals with SCI have a two-fold greater risk of heart disease compared to those without SCI, which is similar to the risk incurred by smoking or diabetes. The increased cardiovascular disease risk in individuals with SCI is often attributed to the increased prevalence of cardiovascular disease risk factors as well as autonomic nervous system dysfunction and physical inactivity. However, individuals with SCI also have stiffer arteries than able-bodied controls with similar age, weight, blood pressure, and physical activity. Arterial stiffness, which is determined by vascular tone and extracellular matrix remodeling, is an independent predictor of cardiovascular risk. Our goal is to understand the mechanisms underlying increased cardiovascular risk in the chronic SCI population. Our preliminary data show that aortic stiffness increases in a mouse SCI model as early as 4 weeks after injury. The change in arterial stiffness may relate to changes in inflammation, sympathetic nervous system activity, and extracellular matrix imbalances. These studies have potential to lead to new cardiovascular treatments in the SCI population and well as in non-SCI patients with systemic inflammation, since arterial stiffness can be readily measured by pulse wave velocity and FDA-approved inflammatory inhibitors are available.





Perfusion effects on cancer metabolism

Tumors have altered metabolism, which is used clinically to identify tumors and is emerging as an important clinical target for cancer therapy. Tumor cells consume more glucose than normal cells and are thought to primarily use glycolysis for energy production even in the presence of oxygen (the Warburg effect). Tumor glycolytic phenotype confers a growth advantage and therefore is a crucial component of cancer progression and malignancy. However, the idea that all tumor cells abide by the Warburg effect has recently come into question. A recent human study demonstrated that poorly perfused tumor regions primarily use glucose for energy production, whereas highly perfused regions primarily use lactate for energy production. The mechanisms underlying the effect of vascular perfusion on tumor metabolic heterogeneity are not fully understood. Our goal is to understand how vascular hemodynamics regulate tumor metabolism. Our preliminary data suggest that fluid flow regulates endothelial glucose metabolism, and that co-culture with endothelial cells alters tumor cell growth and metabolism. In this project, we are creating an engineered vascularized, in vitro breast cancer model to study perfusion-induced changes in tumor metabolism. We will dynamically analyze perfusion-induced changes in endothelial-tumor metabolic interactions using real-time mass spectrometry and mitochondrial fission-fusion analysis. This in vitro model will advance mechanistic understanding of metabolic crosstalk between tumor cells and endothelial cells; uncover potential therapies to treat metabolically heterogeneous tumors; and advance cancer precision medicine.



Vascular glucose transport in traumatic brain injury and Alzheimer’s disease

Glucose transport is highly regulated in the brain and may be dysregulated in traumatic brain injury and Alzheimer’s disease. We are seeking to expand our artery-on-a-chip and vascularized tumor models to examine glucose transport across the blood-brain barrier, as well as metabolic changes in brain endothelial glucose metabolism with mechanical or biochemical injury.

Pressure myography-on-a-chip

Vasoconstriction and vasodilation are essential to blood pressure regulation and physiological responses in health and disease. Vascular contractility can be measured in humans in vivo and in animals ex vivo. Unfortunately human studies require a skilled technician and have limited ability to vary physiological stimuli, whereas animal studies are time consuming and may have limited applicability to human vascular function. While attempts have been made to develop in vitro systems to measure vasoconstriction and vasodilation, these systems do not include circumferentially aligned primary human vascular smooth muscle cells (vSMC) nor do they include perivascular adipose tissue (PVAT), which is critical to arterial response to vasoactive stimuli. Our long-term goal is to understand how PVAT affects arterial function in health and disease. The goal of this project is to create an artery-on-a-chip which includes PVAT and enables vasoconstriction and vasorelaxation measurements in response to both mechanical and biochemical stimuli.

Energy Fields to Control Mitochondrial Metabolism

In the recent times, the response of mitochondria to external energy fields (such as electric, magnetic) are being actively investigated to understand their behaviour when placed under stress. Majority of the research involves compromising the mitochondrial integrity using external energy fields. However, further research needs to be carried out to find non-destructive methods of manipulating mitochondrial morphology to achieve therapeutic purpose. Multiple studies showed that specific energy fields can alter the biochemical and biophysical aspects of mitochondria. This aspect can be utilized to explore possible applications that involve controlling the morphology and motion of mitochondria. The question is which type of energy field yields beneficial morphological changes without damaging the biological properties of mitochondria?  It has been shown that pulse magnetic field and electroporation affects mitochondrial behaviour. However, morphological alterations of mitochondria using these energy fields have not yet been studied thoroughly. To bridge this gap we are investigating a suitable energy field to control the morphology of the mitochondria therefore yielding desirable therapeutic effect.

Contact Information

Call: +1 301 405 7771




Fischell Department of Bioengineering

University of Maryland
4224 A. James Clark Hall 

8278 Paint Branch Drive

College Park, MD 20742

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