Christopher M. Rembold

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Primary Appointment

Clinician Physician RET, Medicine- Cardiovascular Medicine

Research Disciplines

Physiology, Translational Science

Research Interests

Hypertension, Dyslipidemia, Insulin resistance, Sleep apnea, Statistical analysis, Smooth Muscle Contraction/Relaxation, Nitric Oxide

Research Description

1) Activation of blood vessel smooth muscle primarily involves pathways which increase calcium and myosin phosphorylation resulting in contraction.  Most recently my laboratory has been interested in contractile mechanisms beyond calcium and myosin phosphorylation.  Specifically, we found that the sustained phase of contraction was associated with stimulated actin polymerization.  Prior increases in stimulated actin polymerization appear to increase the initial phase of subsequent contraction, a process we term force augmentation.  We are studying the biochemical determinants of stimulated actin polymerization (paxillin and cofilin phosphorylation) and the biophysical sequelae of stimulated actin polymerization (changes in rheology such as noise temperature).  Publications include:

Rembold, C.M.  Force suppression and the crossbridge cycle in swine carotid artery.  American Journal of Physiology Cell Physiology, 293:1003-1009, 2007.
Rembold, C.M., Tejani, A,D. Ripley, M.L., Han, S.  Paxillin phosphorylation, actin polymerization, noise temperature, and the sustained phase of swine carotid artery contraction.  American Journal of Physiology Cell Physiology, 293:993-1002, 2007.
Tejani, A.D., Rembold, C.M.  Force augmentation and stimulated actin polymerization in swine carotid artery.  American Journal of Physiology, in press, 2010.

Relaxation is typically thought to be the reversal of activation, i.e. deactivation, which is caused by a reduction in myosin phosphorylation.  There is also a novel form of smooth muscle relaxation that does not involve deactivation mechanisms. Dr. Rembold's group found that elevations in cyclic nucleotides such as cGMP and cAMP can reduce smooth muscle contraction despite elevated myosin phosphorylation. This process was termed force suppression.  Dr. Rembold's laboratory has concentrated on the mechanism responsible for force suppression. His group and others found that cyclic nucleotide-induced relaxation was associated with phosphorylation of a small heat shock protein 20 known as HSP20 or P20. His group also found that HSP20 phosphorylation was shown to specifically correlate with force suppression rather than the deactivation form of relaxation. A peptide of HSP20 was noted to have sequence homology with troponin I, the main regulatory protein in skeletal and cardiac muscle. The Peptide from this homology region bound thin filaments, reduced myosin ATPase activity, and relaxed skinned swine carotid artery.  We are currently testing the hypothesis that binding of phosphorylated HSP20 to the smooth muscle thin filaments may turn off thin filaments so that phosphorylated myosin does not interact with the thin filament (i.e. a model similar to skeletal muscle troponin I). Publications include:

Rembold C.M., Foster, B., Strauss, J., Wingard, C., Van Eyk, J.E. cGMP mediated phosphorylation of heat shock protein 20 may cause smooth muscle relaxation without myosin light chain dephosphorylation. Journal of Physiology (London), 524:865-878, 2000.
Meeks, M., Ripley, M., Jin, Z. Rembold C.M.,   Heat shock protein 20 mediated force suppression in forskolin relaxed swine carotid artery.  Am J Physiology Cell Physiology,  288:C633-C639, 2005.

3) I also study sleep apnea in children.  Publications include:

Suratt, P.M., Barth, J.T., Diamond, R., DâAndrea, L., Nikova, M., Periello, V.A., Carskadon, M.A., Rembold, C.M.  Reduced Time in Bed and Obstructive Sleep Disordered Breathing in Children are Associated with Cognitive Impairment.  Pediatrics, 119:320-329, 2007.

4) Finally, I also study the use of carotid intimal medial thickness in the detection of preclinical atherosclerosis. Publications include:

Stein, J.H., Korcatz, C.E., Hurst, R.T., Lonn, E., Kendall, C.B., Mohler, E.R., Naijar, S.S. Rembold, C.M., Post, W.S.  Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: A consensus statement from the American society of echocardiography carotid intima-media thickness task force endorsed by the society for vascular medicine.  Journal of the American Society of Echocardiography, 21:93-111, 2008.

Personal Statement

1) Activation of blood vessel smooth muscle primarily involves pathways which increase calcium and myosin phosphorylation resulting in contraction.  Most recently my laboratory has been interested in contractile mechanisms beyond calcium and myosin phosphorylation.  Specifically, we found that the sustained phase of contraction was associated with stimulated actin polymerization.  Prior increases in stimulated actin polymerization appear to increase the initial phase of subsequent contraction, a process we term force augmentation.  We are studying the biochemical determinants of stimulated actin polymerization (paxillin and cofilin phosphorylation) and the biophysical sequelae of stimulated actin polymerization (changes in rheology such as noise temperature).  Publications include:

Rembold, C.M.  Force suppression and the crossbridge cycle in swine carotid artery.  American Journal of Physiology Cell Physiology, 293:1003-1009, 2007.
Rembold, C.M., Tejani, A,D. Ripley, M.L., Han, S.  Paxillin phosphorylation, actin polymerization, noise temperature, and the sustained phase of swine carotid artery contraction.  American Journal of Physiology Cell Physiology, 293:993-1002, 2007.
Tejani, A.D., Rembold, C.M.  Force augmentation and stimulated actin polymerization in swine carotid artery.  American Journal of Physiology, in press, 2010.

2) Relaxation is typically thought to be the reversal of activation, i.e. deactivation, which is caused by a reduction in myosin phosphorylation.  There is also a novel form of smooth muscle relaxation that does not involve deactivation mechanisms. Dr. Rembold's group found that elevations in cyclic nucleotides such as cGMP and cAMP can reduce smooth muscle contraction despite elevated myosin phosphorylation. This process was termed force suppression.  Dr. Rembold's laboratory has concentrated on the mechanism responsible for force suppression. His group and others found that cyclic nucleotide-induced relaxation was associated with phosphorylation of a small heat shock protein 20 known as HSP20 or P20. His group also found that HSP20 phosphorylation was shown to specifically correlate with force suppression rather than the deactivation form of relaxation. A peptide of HSP20 was noted to have sequence homology with troponin I, the main regulatory protein in skeletal and cardiac muscle. The Peptide from this homology region bound thin filaments, reduced myosin ATPase activity, and relaxed skinned swine carotid artery.  We are currently testing the hypothesis that binding of phosphorylated HSP20 to the smooth muscle thin filaments may turn off thin filaments so that phosphorylated myosin does not interact with the thin filament (i.e. a model similar to skeletal muscle troponin I). Publications include:

Rembold C.M., Foster, B., Strauss, J., Wingard, C., Van Eyk, J.E. cGMP mediated phosphorylation of heat shock protein 20 may cause smooth muscle relaxation without myosin light chain dephosphorylation. Journal of Physiology (London), 524:865-878, 2000.
Meeks, M., Ripley, M., Jin, Z. Rembold C.M.,   Heat shock protein 20 mediated force suppression in forskolin relaxed swine carotid artery.  Am J Physiology Cell Physiology,  288:C633-C639, 2005.

3) I also study sleep apnea in children.  Publications include:

Suratt, P.M., Barth, J.T., Diamond, R., DâAndrea, L., Nikova, M., Periello, V.A., Carskadon, M.A., Rembold, C.M.  Reduced Time in Bed and Obstructive Sleep Disordered Breathing in Children are Associated with Cognitive Impairment.  Pediatrics, 119:320-329, 2007.

4) Finally, I also study the use of carotid intimal medial thickness in the detection of preclinical atherosclerosis. Publications include:

Stein, J.H., Korcatz, C.E., Hurst, R.T., Lonn, E., Kendall, C.B., Mohler, E.R., Naijar, S.S. Rembold, C.M., Post, W.S.  Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: A consensus statement from the American society of echocardiography carotid intima-media thickness task force endorsed by the society for vascular medicine.  Journal of the American Society of Echocardiography, 21:93-111, 2008.

Selected Publications

2018

Rembold, C. M. (2018). Coenzyme Q10 Supplementation in Orthostatic Hypotension and Multiple-System Atrophy: A Report on 7 Cases. AMERICAN JOURNAL OF MEDICINE, 131(4), 444-446. doi:10.1016/j.amjmed.2017.10.021

2017

Britton, A. R., Grobbee, D. E., den Ruijter, H. M., Anderson, T. J., Desvarieux, M., Engstrom, G., . . . Bots, M. L. (2017). Alcohol Consumption and Common Carotid Intima-Media Thickness: The USE-IMT Study. ALCOHOL AND ALCOHOLISM, 52(4), 483-486. doi:10.1093/alcalc/agx028

Wang, X., Dalmeijer, G. W., den Ruijter, H. M., Anderson, T. J., Britton, A. R., Dekker, J., . . . Bots, M. L. (2017). Clustering of cardiovascular risk factors and carotid intima-media thickness: The USE-IMT study. PLOS ONE, 12(3). doi:10.1371/journal.pone.0173393

2015

Gijsberts, C. M., Groenewegen, K. A., Hoefer, I. E., Eijkemans, M. J. C., Asselbergs, F. W., Anderson, T. J., . . . den Ruijter, H. M. (2015). Race/Ethnic Differences in the Associations of the Framingham Risk Factors with Carotid IMT and Cardiovascular Events. PLOS ONE, 10(7). doi:10.1371/journal.pone.0132321

Eikendal, A. L. M., Groenewegen, K. A., Anderson, T. J., Britton, A. R., Engstrom, G., Evans, G. W., . . . den Ruijter, H. M. (2015). Common Carotid Intima-Media Thickness Relates to Cardiovascular Events in Adults Aged <45 Years. HYPERTENSION, 65(4), 707-+. doi:10.1161/HYPERTENSIONAHA.114.04658

2014

van den Oever, I. A. M., Nurmohamed, M. T., & Lems, W. F. (2014). Niacin for Reduction of Cardiovascular Risk. NEW ENGLAND JOURNAL OF MEDICINE, 371(20), 1942.

Santos-Gallego, C. G., & Badimon, J. (2014). Niacin for Reduction of Cardiovascular Risk. NEW ENGLAND JOURNAL OF MEDICINE, 371(20), 1943.

Landray, M. J., Haynes, R., & Armitage, J. (2014). Niacin for Reduction of Cardiovascular Risk REPLY. NEW ENGLAND JOURNAL OF MEDICINE, 371(20), 1943-1944.

Mayer, L. (2014). Niacin for Reduction of Cardiovascular Risk. NEW ENGLAND JOURNAL OF MEDICINE, 371(20), 1943.

Meneses, F. (2014). Niacin for Reduction of Cardiovascular Risk. NEW ENGLAND JOURNAL OF MEDICINE, 371(20), 1941.

Hu, M., & Tomlinson, B. (2014). Niacin for Reduction of Cardiovascular Risk. NEW ENGLAND JOURNAL OF MEDICINE, 371(20), 1941-1942.

Rembold, C. M. (2014). Niacin for Reduction of Cardiovascular Risk. NEW ENGLAND JOURNAL OF MEDICINE, 371(20), 1940-1941. doi:10.1056/NEJMc1411240

Hedegaard, E. R., Nielsen, B. D., Mogensen, S., Rembold, C. M., Frobert, O., & Simonsen, U. (2014). Mechanisms involved in increased sensitivity to adenosine A2A receptor activation and hypoxia-induced vasodilatation in porcine coronary arteries. EUROPEAN JOURNAL OF PHARMACOLOGY, 723, 216-226. doi:10.1016/j.ejphar.2013.11.029

Bots, M. L., Groenewegen, K. A., Anderson, T. J., Britton, A. R., Dekker, J. M., Engstrom, G., . . . den Ruijter, H. M. (2014). Common Carotid Intima-Media Thickness Measurements Do Not Improve Cardiovascular Risk Prediction in Individuals With Elevated Blood Pressure The USE-IMT Collaboration. HYPERTENSION, 63(6), 1173-1181. doi:10.1161/HYPERTENSIONAHA.113.02683

Rembold, C. M., & Suratt, P. M. (2014). Airway turbulence and changes in upper airway hydraulic diameter can be estimated from the intensity of high frequency inspiratory sounds in sleeping adults. JOURNAL OF PHYSIOLOGY-LONDON, 592(17), 3831-3839. doi:10.1113/jphysiol.2014.272302

Okutsu, M., Call, J. A., Lira, V. A., Zhang, M., Donet, J. A., French, B. A., . . . Yan, Z. (2014). Extracellular Superoxide Dismutase Ameliorates Skeletal Muscle Abnormalities, Cachexia, and Exercise Intolerance in Mice with Congestive Heart Failure. CIRCULATION-HEART FAILURE, 7(3), 519-U268. doi:10.1161/CIRCHEARTFAILURE.113.000841

2013

Rembold, C. M. (2013). Review: Vitamin and antioxidant supplements do not prevent adverse cardiovascular events. ANNALS OF INTERNAL MEDICINE, 158(12). doi:10.7326/0003-4819-158-12-201306180-02010

den Ruijter, H. M., Peters, S. A. E., Groenewegen, K. A., Anderson, T. J., Britton, A. R., Dekker, J. M., . . . Bots, M. L. (2013). Common carotid intima-media thickness does not add to Framingham risk score in individuals with diabetes mellitus: the USE-IMT initiative. DIABETOLOGIA, 56(7), 1494-1502. doi:10.1007/s00125-013-2898-9

Rembold, C. M., Garvey, S. M., & Tejani, A. D. (2013). Slack Length Reduces the Contractile Phenotype of the Swine Carotid Artery. JOURNAL OF VASCULAR RESEARCH, 50(3), 221-227. doi:10.1159/000350823

2012

Den Ruijter, H. M., Peters, S. A. E., Anderson, T. J., Britton, A. R., Dekker, J. M., Eijkemans, M. J., . . . Bots, M. L. (2012). Common Carotid Intima-Media Thickness Measurements in Cardiovascular Risk Prediction A Meta-analysis. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 308(8), 796-803. doi:10.1001/jama.2012.9630

Chen, A. F., Chen, D. -D., Daiber, A., Faraci, F. M., Li, H., Rembold, C. M., & Laher, I. (2012). Free radical biology of the cardiovascular system. CLINICAL SCIENCE, 123(1-2), 73-91. doi:10.1042/CS20110562

Rembold, C. M. (2012). Review: Aspirin does not reduce CHD or cancer mortality but increases bleeding. ANNALS OF INTERNAL MEDICINE, 156(12). doi:10.7326/0003-4819-156-12-201206190-02003

2011

Lee, M. Y., Garvey, S. M., Ripley, M. L., & Wamhoff, B. R. (2011). Genome-Wide Microarray Analyses Identify the Protein C Receptor as a Novel Calcineurin/Nuclear Factor of Activated T Cells-Dependent Gene in Vascular Smooth Muscle Cell Phenotypic Modulation. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 31(11), 2665-U768. doi:10.1161/ATVBAHA.111.235960

Tejani, A. D., Walsh, M. P., & Rembold, C. M. (2011). Tissue length modulates "stimulated actin polymerization," force augmentation, and the rate of swine carotid arterial contraction. AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 301(6), C1470-C1478. doi:10.1152/ajpcell.00149.2011

Suratt, P. M., Diamond, R., Barth, J. T., Nikova, M., & Rembold, C. (2011). Movements during sleep correlate with Impaired Attention and Verbal and Memory Skills in children with adenotonsillar hypertrophy suspected of having obstructive sleep disordered breathing. SLEEP MEDICINE, 12(4), 322-328. doi:10.1016/j.sleep.2010.10.007

2010

Rembold, C. M., & Tejani, A. (2010). Stimulated Actin Polymerization Induces Force Potentiation in Swine Carotid Artery. Biophysical Journal, 98(3), 355a. doi:10.1016/j.bpj.2009.12.1917

Stein, J. H., Korcarz, C. E., Hurst, R. T., Lonn, E., Kendall, C. B., Mohler, E. R., . . . Post, W. S. (2010). Noninvasive Assessment of Subclinical Atherosclerosis in Children and Adolescents: Recommendations for Standard Assessment for Clinical Research: A Scientific Statement From the American Heart Association (vol 54, pg 919, 2009). HYPERTENSION, 56(3), E36. doi:10.1161/HYP.0b013e3181efaa67

Tejani, A. D., & Rembold, C. M. (2010). Force augmentation and stimulated actin polymerization in swine carotid artery. AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 298(1), C182-C190. doi:10.1152/ajpcell.00326.2009