My primary research focus is vascular aging, in particular the cellular, molecular and tissue specific events that induce reductions in muscle blood flow during exercise, impair arterial endothelial function and stiffen large elastic arteries in older rodents/adults. These vascular phenotypes contribute to the age related decline in functional capacity and the development of cardiovascular disease, and can be ameliorated by lifestyle interventions such as habitual exercise and caloric restriction. My secondary focus, is to elucidate the cellular pathways which confer the vaso-protective effects of these lifestyle interventions and try to activate these pathways pharmacologically to see if this will confer some of the same benefits. I have used human, rodent, and cell models to address these questions and utilized a wide range of contemporary translational experimental techniques from microRNA gene expression to ultrasonography to investigate the aforementioned interests.
University of Colorado, Department of Integrative Physiology
University of California at San Diego, Department of Medicine, Dr. Russell Richardson
Texas A&M University
University of Colorado, Boulder
University of Colorado, Boulder
- Bloom SI, Liu Y, Tucker JR, Islam MT, Machin DR, Abdeahad H, Thomas TG, Bramwell RC, Lesniewski LA, Donato AJ (2023). Endothelial cell telomere dysfunction induces senescence and results in vascular and metabolic impairments. Aging Cell, e13875.
- Gogulamudi VR, Islam MT, Durrant JR, Adeyemo AO, Trott DW, Hyuhn MH, Zhu W, Donato AJ, Walker AE, Lesniewski LA (2023). Heterozygosity for ADP-ribosylation factor 6 suppresses the burden and severity of atherosclerosis. PLoS One, 18(5), e0285253.
- Machin DR, Trott DW, Gogulamudi VR, Islam MT, Bloom SI, Vink H, Lesniewski LA, Donato AJ (2023). Glycocalyx-targeted therapy ameliorates age-related arterial dysfunction. Geroscience.
- Islam MT, Tuday E, Allen S, Kim J, Trott DW, Holland WL, Donato AJ, Lesniewski LA (2023). Senolytic drugs, dasatinib and quercetin, attenuate adipose tissue inflammation, and ameliorate metabolic function in old age. Aging Cell, 22(2), e13767.
- Lim J, Machin DR, Donato AJ (2023). The role of hyaluronan in endothelial glycocalyx and potential preventative lifestyle strategy with advancing age. Curr Top Membr, 91, 139-156.
- Frech TM, Maguire C, Petrey AC, Stoddard GJ, Donato AJ (2022). A systemic sclerosis disease model: can inducible pluripotent stem cells fill an unmet need in defining vascular leak? Rheumatology (Oxford).
- Bloom SI, Tucker JR, Lim J, Thomas TG, Stoddard GJ, Lesniewski LA, Donato AJ (2022). Aging results in DNA damage and telomere dysfunction that is greater in endothelial versus vascular smooth muscle cells and is exacerbated in atheroprone regions. Geroscience, 44(6), 2741-2755.
- Mankouski A, Miller TA, Dodson RB, Yu B, Yang Y, Liu J, Machin DR, Donato AJ, McKnight RA, Zinkhan EK (2022). Large artery stiffening and mortality in a rat model of early vascular remodeling induced by intrauterine growth restriction and a high-fat diet. Physiol Rep, 10(23), e15518.
- Gogulamudi VR, Machin DR, Henson GD, Lim J, Bramwell RC, Durrant JR, Donato AJ, Lesniewski LA (2022). Sirt1 overexpression attenuates Western-style diet-induced aortic stiffening in mice. Physiol Rep, 10(9), e15284.
- Machin DR, Clifton HL, Wray DW, Frech TM, Donato AJ (2022). Tetrahydrobiopterin Administration Augments Exercise-Induced Hyperemia and Endothelial Function in Patients With Systemic Sclerosis. Front Med (Lausanne), 8, 791689.
- Pierce GL, Coutinho TA, DuBose LE, Donato AJ (2021). Is It Good to Have a Stiff Aorta with Aging? Causes and Consequences. Physiology (Bethesda).
- Trott DW, Machin DR, Phuong TT, Adeyemo AO, Bloom SI, Bramwell RC, Sorensen ES, Lesniewski LA, Donato AJ (2021). T cells mediate cell non-autonomous arterial aging in mice. J Physiol, 599, 3973-3991.
- Trott DW, Islam MT, Buckley DJ, Donato AJ, Dutson T, Sorensen ES, Cai J, Gogulamudi VR, Phuong TTT, Lesniewski LA (2021). T lymphocyte depletion ameliorates age-related metabolic impairments in mice. Geroscience, 43(3), 1331-1347.
- Islam MT, Henson GD, Machin DR, Bramwell RC, Donato AJ, Lesniewski LA (2020). Aging differentially impacts vasodilation and angiogenesis in arteries from the white and brown adipose tissues. Exp Gerontol, 142, 111126.
- Machin DR, Auduong Y, Gogulamudi VR, Liu Y, Islam MT, Lesniewski LA, Donato AJ (2020). Lifelong SIRT-1 overexpression attenuates large artery stiffening with advancing age. Aging (Albany NY), 12(12), 11314-11324.
- Phuong TTT, Walker AE, Henson GD, Machin DR, Li DY, Donato AJ, Lesniewski LA (2019). Deletion of Robo4 prevents high-fat diet-induced adipose artery and systemic metabolic dysfunction. Microcirculation, 26(5), e12540.
- Ait-Aissa K, Blaszak SC, Beutner G, Tsaih SW, Morgan G, Santos JH, Flister MJ, Joyce DL, Camara AKS, Gutterman DD, Donato AJ, Porter GA Jr, Beyer AM (2019). Mitochondrial Oxidative Phosphorylation defect in the Heart of Subjects with Coronary Artery Disease. Sci Rep, 9(1), 7623.
- Yuen LH, Dana S, Liu Y, Bloom SI, Thorsell AG, Neri D, Donato AJ, Kireev D, Schler H, Franzini RM (2019). A Focused DNA-Encoded Chemical Library for the Discovery of Inhibitors of NAD+-Dependent Enzymes. J Am Chem Soc, 141(13), 5169-5181.
- Machin DR, Phuong TT, Donato AJ (2019). The role of the endothelial glycocalyx in advanced age and cardiovascular disease. Curr Opin Pharmacol, 45, 66-71.
- Walker AE, Kronquist EK, Chinen KT, Reihl KD, Li DY, Lesniewski LA, Donato AJ (2019). Cerebral and skeletal muscle feed artery vasoconstrictor responses in a mouse model with greater large elastic artery stiffness. Exp Physiol, 104(3), 434-442.
- Hazra S, Henson GD, Bramwell RC, Donato AJ, Lesniewski LA (2019). Impact of high-fat diet on vasoconstrictor reactivity of white and brown adipose tissue resistance arteries. Am J Physiol Heart Circ Physiol, 316(3), H485-H494.
- Walker AE, Breevoort SR, Durrant JR, Liu Y, Machin DR, Dobson PS, Nielson EI, Meza AJ, Islam MT, Donato AJ, Lesniewski LA (2019). The pro-atherogenic response to disturbed blood flow is increased by a western diet, but not by old age. Sci Rep, 9(1), 2925.
- Bloom SI, Islam MT, Lesniewski LA, Donato AJ (2022). Mechanisms and consequences of endothelial cell senescence. [Review]. Nat Rev Cardiol, 20(1), 38-51.