200 Lothrop Street
B.S. Biochemistry, University of Missouri - Columbia
M.D. Saint Louis University School of Medicine
The predominant interest of the lab is in in the biological process of arteriogenesis. In patients with arterial occlusive disease, arteriogenesis is an adaptive process of creating collateral vessels that function to keep ischemic tissues viable. In other words, when the ‘highways’ become jammed (occlusion of a conductance vessel), ‘backroads’ open to serve as ‘detours’ for blood flow (branch arteries remodel, expand and become collaterals). Unfortunately, it seems as though the natural equilibrium tends to halt the growth of collaterals early, when only around 40% capacitance of the occluded conductance vessel is achieved.
Arteriogenesis represents an exciting area of potential medical therapy for unreconstructable vascular disease. If this natural process could be pushed further, a medical alternative to surgical or interventional revascularization may be found. Currently, it is accepted that hemodynamic forces result in the initial stimulus for collateral formation, but early biochemical signaling pathways are not well understood. Purinergic signaling is a tightly regulated system of receptors, extracellular purine nucleotides, and hydrolyzing enzymes, which is likely relevant in arteriogenesis but has not been studied to date. Specifically, the lab investigates the role of purinergic signaling as an early mediator of arteriogenesis.
P2Y2 Nucleotide Receptor Mediates Arteriogenesis in a Murine Model of Hindlimb Ischemia. McEnaney RM, Shukla A, Madigan MC, Sachdev U, Tzeng E. J Vasc Surg. 2014; pii: S0741-5214(14)01281-6. [Epub ahead of print]. PMID: 25088742
TLR2 and TLR4 Mediate Differential Responses to Hindlimb Ischemia Through MyD88-Dependent and Independent Pathways. Sachdev U, Cui X, McEnaney R, Wang T, Benabou K, Tzeng E. PLoS One. 2012;7(11): e50654 PMID: 23209800