Douglas K. Bowles, PhD

Douglas K. Bowles

  • Professor & Chair
  • Investigator, Dalton Cardiovascular Research Center
  • PhD: University of Texas at Austin
  • Postdoctoral: University of Missouri-Columbia
  • Research: The role of ion channels in cardiovascular disease
  • Teaching: Cell Biology, Physiology

 

Dr. Bowles focuses his research on the role of ion channels in the heart and coronary arteries. The goal of Dr. Bowles’ research is to determine the molecular mechanisms underlying the contribution of vascular smooth muscle (VSM) in the development of atherosclerotic plaque and the mechanisms by which plaque composition may be altered. The lab’s approach is vertically integrated, progressing from molecular mechanisms of gene expression, to murine transgenic models to clinical measures of coronary artery disease (CAD) in mouse and swine models of atherosclerosis. This approach spans in vitro knockdown/overexpression to cell electrophysiology to catheter-based coronary intervention involving coronary angiography, intravascular ultrasound (IVUS) and vascular gene therapy (i.e. molecular silencing/overexpression). To enhance translational application, the lab has become “swine interventional cardiologists”. This has allowed lab members to apply human CAD assessment approaches, e.g. IVUS and quantitative angiography in the swine, to pursue the mechanistic bases in a model of true CAD. The lab also uses mouse transgenic models of atherosclerosis to determine candidate gene causality.

A complete list of publications on PubMed can be found here

Bowles, D.K., M.H. Laughlin and M. Sturek. Exercise training increases L-type calcium current density in coronary smooth muscle. J. Physiol. (Heart Circ. Physiol. 44):H2159-H2169, 1998. PMID: 9843816

Bowles, D.K. Adaptation of ion channels in the microcirculation to exercise training. Microcirculation, 7:25-40, 2000. PMID: 10708335

Wamhoff, B., N.J. Dietz, K. Bowles and M. Sturek. Exercise training attenuates coronary smooth muscle phenotypic modulation and nuclear Ca2+ signaling.  Am.  J.  Physiol. Heart Circ.  Physiol. 283: H2397-H2410, 2002. PMID: 12388302

Bowles, D.K., C.L. Heaps, J. Turk, K.K. Maddali and E. M. Price. Hypercholesterolemia inhibits L-type calcium current in coronary macro, not microcirculation. Appl. Physiol. 96: 2240-2248, 2004. PMID: 14752123

Bowles, D.K., V.K. Ganjam, K.K. Maddali, L.J. Rubin, D.L. Tharp, J.R. Turk and C.L. Heaps. Endogenous testosterone increases L-type Ca2+ channel expression in porcine coronary smooth muscle. J. Physiol. (Heart Circ. Physiol). 287: H2091-H2098, 2004. PMID: 15242831

Wamhoff, B.R., K. Bowles and G.K. Owens. Excitation-transcription coupling in vascular smooth muscle. Circ. Res. 98 868-878, 2006. PMID: 16614312

Sinha, S., B.R. Wamhoff, M.H. Hoofnagle, J. Thomas, R.L. Neppl, T. Deering, B. Helmke, K. Bowles, A.V. Somlyo, G.K. Owens. Assessment of Contractility of Purified Smooth Muscle Cells Derived from Embryonic Stem Cells. Stem Cells. 24(7):1678-88, 2006. PMID: 16601077

Tharp, D.L., B.R. Wamhoff, J.R. Turk and K. Bowles. Upregulation of intermediate-conductance, Ca2+-activated K+ channel (IKCa1) mediates phenotypic modulation of coronary smooth muscle. Am. J. Physiol. (Heart Circ. Physiol). 291: 2493-2503, 2006. PMID: 16798818

Tharp, D.L., B.R. Wamhoff, H. Wulff, G. Raman, A. Cheong and K. Bowles. Local delivery of the KCa3.1 blocker, TRAM-34, prevents acute angioplasty-induced coronary smooth muscle phenotypic modulation and limits stenosis. Atherosclerosis Thrombosis and Vascular Biology. 28:1084-1089, 2008. PMID: 18309114

Phillips, L.C., A.L. Klibanov, K. Bowles, M. Ragosta, J. A. Hossack and B.R. Wamhoff. Focused In Vivo Delivery of plasmid DNA to the Porcine Vascular Wall via Intravascular Ultrasound (IVUS) Destruction of Microbubbles. J. Vasc. Res. 47(3):270-274, 2010. PMID: 19923850

Emter, C.A. and K. Bowles. Store-operated Ca2+ entry is not essential for PDGF-BB induced phenotype modulation or upregulation of intermediate-conductance Ca2+-activated K+ channel (KCa3.1) in rat aortic smooth muscle. Cell Calcium. 48(1):10-18, 2010. PMID: 20619453

Bowles, D.K. and M.H. Laughlin. Mechanisms of beneficial effects of Physical Activity on Atherosclerosis and Coronary Heart Disease. Appl. Physiol. 111(1):308-10, 2011. PMID:2161708

Emter, C.A., D.L. Tharp, J.R. Ivey, V.K. Ganjam and K. Bowles. Low-Intensity Interval Exercise Training Attenuates Heart Failure Induced Alterations in Coronary Vascular Function in Aortic-Banded Miniature Swine. Am. J. Physiol. (Heart Circ. Physiol). 301(4):H1687-94, 2011. PMID:21841018

Heaps, C.L., D.L. Tharp and D.K. Bowles. Hypercholesterolemia abolishes voltage-dependent K+ channel contribution to adenosine-mediated relaxation in porcine coronary arterioles. Am. J. Physiol. (Heart Circ. Physiol). In press: 10.1152/ajpheart.00157.2004.

O’Connor, E.K., J.R. Ivey and D.K. Bowles. Differential effects of androgens on coronary blood flow regulation and arteriolar diameter in intact and castrated swine. Biol. Sex Differences. 3(1):10, 2012. PMID:22620281

Masseau, I., M.J. Davis and D.K. Bowles. Carotid Inflammation Is Unaltered by Exercise in Hypercholesterolemic Swine. Med. Sci. Sport Med., 44(12):2277-89, 2012. PMID:22776877

Tharp, D.L, J.R. Ivey, R.L. Shaw and D.K. Bowles. Ovariectomy increases L-type Ca2+ channel activity in porcine coronary smooth muscle. Menopause. 21(6): 661-8, 2014. PMID:24104606

Gole, H.K.A., D.L. Tharp and D.K. Bowles. Upregulation of intermediate-conductance Ca2+-activated K+ channels (KCNN4) in porcine coronary smooth muscle requires NADPH oxidase 5 (NOX5). PLOS ONE 9(8): e105337, 2014. PMID:25144362

Masseau, I. and D.K. Bowles. Carotid endothelial VCAM-1 is an early marker of carotid atherosclerosis and predicts coronary artery disease in swine. Journal of Biomedical Science and Engineering. 8:(11): 789-96, 2015. PMID:26702331

Bender, S.B., V.J. de Beer, D.L. Tharp, D.K. Bowles, M.H. Laughlin, D. Merkus and D.J. Duncker. Severe familial hypercholesterolemia impairs the regulation of coronary blood flow and oxygen supply during exercise. Basic Res. Cardiol. 111(6):61, 2016. PMID:27624732

Tharp, D.L., I. Masseau, J. Ivey, M.H. Laughlin and K. Bowles. Exercise training does not limit coronary atherosclerosis in familial hypercholesterolemic swine. Physiol Rep. 7(4), 2019, e14008. doi: 10.14814/PHY2.14008. PMID: 30809955

Bowles, D.K. and D.L. Tharp. KCa1 inhibition decreases size and alters composition of atherosclerotic lesions induced by low, oscillatory flow. Artery Research. 27(2), 93-100, 2021, PMID: 34457083.

Goodwill, A.G., H.E. Baker, G.M. Dick, P.E. McCallinhart, C.A. Bailey, S.M. Brown, J.J. Man, D.L. Tharp, H.E. Clark, B.S. Blaettner, I.Z. Jaffe, K. Bowles, A.J. Trask, J.D. Tune, and S.B. Bender. Mineralocorticoid receptor blockade normalizes coronary resistance in obese swine independent of functional alterations in Kv channels. Basic Res. in Cardiology. 2021 May 20;116(1):35. PMID: 34018061

Active

1 R01HL151444-A1 (Bowles, PI) 4/1/22-3/31/26
NIH/NHLBI
Cell-specific role and therapeutic potential of KCa3.1 in atherosclerosis
Major goals: To determine the role and underlying mechanism(s) by which the intermediate conductance, Ca2+-activated K+ channel, KCa3.1 (encoded by Kcnn4), dictates migration of vascular smooth muscle and the consequent effect on atherosclerotic lesion formation and composition
Role: PI