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.
Education History
Postdoctoral Fellowship |
University of Colorado, Department of Integrative Physiology |
Postdoctoral Fellow |
---|---|---|
University of California at San Diego, Department of Medicine, Dr. Russell Richardson |
Postdoctoral Fellow | |
Doctoral Training |
Texas A&M University |
PhD |
University of Colorado, Boulder |
MS | |
Undergraduate |
University of Colorado, Boulder |
BA |
Selected Publications
Journal Article
- Gimblet CJ, Ernst JW, Bell B, Bos KD, Stroud AK, Wendt LH, Donato AJ, Jalal DI, Pierce GL (2024). Effect of glycocalyx-targeted therapy on vascular function in older adults: a randomized controlled trial. J Appl Physiol Respir Environ Exerc Physiol, 136(6), 1488-1495. (Read full article)
- Islam MT, Cai J, Allen S, Moreno DG, Bloom SI, Bramwell RC, Mitton J, Horn AG, Zhu W, Donato AJ, Holland WL, Lesniewski LA (2024). Endothelial-Specific Reduction in Arf6 Impairs Insulin-Stimulated Vasodilation and Skeletal Muscle Blood Flow Resulting in Systemic Insulin Resistance in Mice. Arterioscler Thromb Vasc Biol, 44(5), 1101-1113. (Read full article)
- Venturelli M, Morgan GR, Tarperi C, Zhao J, Naro F, Reggiani C, Donato AJ, Richardson RS, Schena F (2024). Physiological determinants of mechanical efficiency during advanced ageing and disuse. J Physiol, 602(2), 355-372. (Read full article)
- Gimblet CJ, Ernst JW, Bos KD, Stroud AK, Donato AJ, Jalal DI, Pierce GL (2023). Effect of acute heparin administration on glycocalyx thickness and endothelial function in healthy younger adults. J Appl Physiol Respir Environ Exerc Physiol. (Read full article)
- Islam MT, Hall SA, Dutson T, Bloom SI, Bramwell RC, Kim J, Tucker JR, Machin DR, Donato AJ, Lesniewski LA (2023). Endothelial cell-specific reduction in mTOR ameliorates age-related arterial and metabolic dysfunction. Aging Cell, 23(2), e14040. (Read full article)
- Bloom SI, Tucker JR, Machin DR, Abdeahad H, Adeyemo AO, Thomas TG, Bramwell RC, Lesniewski LA, Donato AJ (2023). Reduction of double-strand DNA break repair exacerbates vascular aging. Aging (Albany NY), 15(19), 9913-9947. (Read full article)
- 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, 22(8), e13875. (Read full article)
- 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. (Read full article)
- 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. (Read full article)
- 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. (Read full article)
- 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. (Read full article)
- 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). (Read full article)
- 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. (Read full article)
- 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. (Read full article)
- 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. (Read full article)
- 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. (Read full article)
- Pierce GL, Coutinho TA, DuBose LE, Donato AJ (2021). Is It Good to Have a Stiff Aorta with Aging? Causes and Consequences. Physiology (Bethesda). (Read full article)
- 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. (Read full article)
- 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. (Read full article)
- 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. (Read full article)
- 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. (Read full article)
- 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. (Read full article)
- 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. (Read full article)
- 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. (Read full article)
- 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. (Read full article)
- 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. (Read full article)
- 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. (Read full article)
- 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. (Read full article)
Review
- Machin DR, Sabouri M, Zheng X, Donato AJ (2023). Therapeutic strategies targeting the endothelial glycocalyx. [Review]. Curr Opin Clin Nutr Metab Care, 26(6), 543-550. (Read full article)
- Bloom SI, Islam MT, Lesniewski LA, Donato AJ (2022). Mechanisms and consequences of endothelial cell senescence. [Review]. Nat Rev Cardiol, 20(1), 38-51. (Read full article)