 |
Mohammed A. Nayeem, Ph.D. |
Assistant Professor in Physiology and Pharmacology
Graduate Training: Osmania University, Hyderabad, India
Fellowships: Medical College of Virginia/Virginia Commonwealth University,
NRSA/NIH and NIEHS/NIH/DHHS. |
|
Office: 220-BBRF
Lab: 256 & 270-BBRF
PO Box 9229
Morgantown, WV 26506 |
Email: mnayeem@hsc.wvu.edu
Phone: 304-293-4484
Fax: 304-293-3850 |
Research Interest:
The search for potential factors modifying the pathogenesis and course of vascular diseases remains a major goal in cardiovascular medicine. Adenosine plays an important role in the maintenance of vascular tone via activation of four receptor (A1, A2A, A2B, and A3) subtypes. In blood vessels, vasodilation is primarily caused by the activation of A2A AR. Surveys of cytochrome P450 expression among populations have shown that there is a strong coordinative link between levels of expression of some CYP enzymes and the presence of cardiovascular disease, such as hypertension, coronary artery disease, myocardial infarction, heart failure, stroke, cardiomyopathy and arrhythmias. Evidence of some defective alleles of CYP epoxygenases have been shown to exist commonly in various Asian populations, and these genetic variations in the CYP epoxygenase pathway have been suggested to be associated with development of atherosclerosis and hypertension. Elimination of the anti-pressor action of EETs led to marked elevation of mean arterial pressure produced by deletion of A2A AR in knockout mice (A2A AR-/-). Further, sEH expression is increased in the pre-hypertensive stage (3 weeks of age) and hypertertensive stage (9 weeks of age) in spontaneously hypertensive (SHR) rats as compared with non-hypertensive Wistar-Kyoto (WKY) rats. Also, the targeted disruption of the sEH gene in male mice lowers systolic blood pressure. Our laboratory is interested in understanding the mechanism of vascular contraction leading to increase in mean arterial pressure in mice through absence or downregulation of A2A AR via CYP epoxygenases /sEH signaling pathway using COX-1-/-, COX-2-/-, eNOS-/-, A2A AR-/-, sEH-/-, CYP2J2-overexpressed, sEH-overexpressed and their respective wild-type mice. Our laboratory is also interested in understanding the mechanism of development of hypertension in both high salt (HS) and normal salt (NS)-diet fed mice through A2A AR via CYP epoxygenases /sEH signaling pathway. We believe the identification of this signaling pathway will help to unravel the potential mechanism involved arachidonic acids and adenosine receptors in vascular contraction. This laboratory is one of the very few laboratories that have established a correlation between CYP450s and adenosine receptors.
The long-term goal of this laboratory is to identify and develop novel pharmacological agents to therapeutically target essential as well as salt-sensitive hypertension in humans. We are collaborating with nationally and internationally well established investigators like: Dr. Falck (UTSWMC, Dallas, TX), Dr. Zeldin (NIEHS /NIH, RTP, NC), Dr. Poloyac (UP, Pittsburgh, PA), Dr. Morisseau (UCLA, California) and Dr. Marowsky (IPT, Zurich, Switzerland). This laboratory is one of the very few laboratories that have established a correlation between CYP450s and adenosine receptors.
Our laboratory is interested in understanding the cellular and molecular mechanisms involved in vascular tone regulation and salt-sensitivity. Specific research areas are:
- Role of adenosine receptors in the regulation of vascular tone through CYP epoxygenases, soluble epoxide hydrolase and omega hydroxylase
- The regulation of vascular tone through the generation of EETs, DHETs and 20-HETE
- The regulation of vascular tone through the adenylyl cyclase cAMP and PKA signaling.
- The regulation of vascular tone through peroxisome proliferator-activated receptors (PPARs)
- The regulation of vascular tone through ATP-sensitive (KATP) channels.
|
|
|
|
 |
Fig. 1: Actual tracings of relaxation/contraction responses to ACh, adenosine 5'-N-ethylcarboxamide (NECA), and CGS-21680 in phenylephrine (PE)-preconstricted A2A adenosine receptor (A2AAR) knockout (A2AAR–/–) and wild-type (A2AAR+/+) mouse aortic rings. |
|
Fig. 2: Effect of L-NAME (100 µM) on acetylcholine induced vascular response in aortic rings of mice fed NS and HS containing diet. Values are mean ± SEM. *p < 0.05 between HS and NS vs. NS+L-NAME and HS +L-NAME. |
|
Fig.3: CGS 21680-induced vascular responses in aortic rings of mice fed NS containing diet and HS containing diet. Values are mean ± SEM. *p < 0.05 compared to NS. |
| |
|
|
|
|
|
|
|
|
|
Fig.4: Representative western blots and densitometric data for CYP2J2 protein in aortas of eNOS+/+ and eNOS-/- mice fed with HS and NS containing diets. Values are mean ± SEM, *#p < 0.05 compared NS (eNOS+/+, eNOS-/-) aortas with *HS (eNOS+/+) and #HS (eNOS-/-). |
|
Fig.5: Representative western blots and densitometric data for sEH protein in aortas of eNOS+/+ and eNOS-/- mice fed with HS and NS containing diets. Values are mean ± SEM, *#p < 0.05 compared NS (eNOS+/+, eNOS-/-) aortas with *HS (eNOS+/+) and #HS (eNOS-/-). |
|
|
|
Selected Publications:
- Hoag, J.B., Qian, Y.Z., Nayeem, M.A., Angelo, M.D., and Kukreja, R.C. ATP-Sensitive Potassium Channel Mediates Delayed Ischemic Protection by Heat Stress in Rabbit Heart: American Journal of Physiology (Heart and Circulatory Physiology) 42: H2458-H2464, 1997. Pubmed
- Nayeem, M.A., Elliott, G.T., Shah, M.R., Hastillo-Hess, S.L and Kukreja, R.C Monophosphoryl lipid A Protects Adult Rat Cardiac Myocytes with Induction of The 72-k D Heat Shock Protein: A Cellular Model of Pharmacologic Preconditioning. Journal of Molecular and Cellular Cardiology 29: 2305-2310, 1997. Pubmed
- Nayeem, M.A., Hess, M.L., Qian, Y.Z., Loesser, K.E., and Kukreja, R.C. Delayed Preconditioning of Cultured Adult Rat Cardiac Myocytes: Role of 70 and 90 k D Heat Stress Protein. American Journal of Physiology (Heart and Circulatory Physiology) 42 (2): H861-H868, 1997. Pubmed
- Nayeem, M.A., Ho, Y, S., Chelliah, J., Hess, M.L., and Kukreja, R.C. Myocytes Derived From Transgenic Mice Overexpressing Glutathione Peroxidase Resist “Lethal” Heat Shock Injury via Opening of KATP Channel. Circulation, 96 (8): I-312, 1997.
- Xi, L., Chelliah, J., Nayeem, M.A., Levasseur, J.E., Hess, M.L and Kukreja, R.C. Whole Body Heat Shock Fails to Protect Mouse Heart Against Ischemia/Reperfusion Injury: Lack of Correlation for 72 kD a Heat Shock Protein in Myocardial Protection. Journal of Molecular and Cellular Cardiology, 30 (11): 2213-2227, 1998. Pubmed
- Kukreja, R.C., Qian, Y-Z, Bernardo, N.L., Nayeem, M.A., and Chelliah, J. Does heat shock protein 72 play a role in second window of preconditioning in heart? A rat study. Circulation, 98 (17): I-621, 1998.
- Nayeem, M.A., Matherne P.G., Hess, M.L., and Kukreja, R.C. Myocytes derived from transgenic mice Overexpressing A1 receptor resist ischemic injury via opening KATP channel. Circulation, 98 (17): I-417-418, 1998.
- Nayeem, M.A., Matherne P.G., Chelliah, J., Hess, M.L., and Kukreja, R.C. Evidence that opening of KATP channel is the common mechanism of protection in heat stressed and transgenic mice myocytes overexpressing A1 adenosine receptor. Circulation, 98 (17): I-344, 1998.
- Qian, Y-Z, Bernardo, N.L., Nayeem, M.A., Chelliah, J and Kukreja, R.C. Does heat shock protein 72 play a role in second window of preconditioning in heart? A rat study. American Journal of Physiology (Heart and Circulatory Physiology), 276 (1 Pt 2): H224-H234, 1999.
- Nayeem, M.A., Olanrewaju, H.A., and Mustafa S.J. Chronic Salt Loading and the Expression of Adenosine Receptor Subtypes (Letter to the Editor). Hypertension, 34 (6): e18-9, 1999. Pubmed
- Nayeem, M.A.,Matherne, G.P and Mustafa, S.J. A1 Adenosine Receptor Agonists 2-Chloro-N6-cyclopentyladenosine (CCPA) and (2S)-N6-[2- endo-Norbornyl] adenosine (S-ENBA) Enhances Late Cellular Protection in A1 Receptor Overexpressed Transgenic Mice Myocytes against Simulated ischemia. Circulation, 102 (18): II-269-270, 2000.
- Nayeem, M.A., and Mustafa S.J. Mechanisms of Delayed Preconditioning by A1adenosine receptor in Porcine Coronary Smooth Muscle Cells. Polish Journal Pharmacology, 54: 443-453, 2002. Pubmed
- Nayeem, M.A., and Mustafa S.J. Regulation of Protein Kinase C by A1 Adenosine Receptor in Porcine Coronary Smooth Muscle Cells. Vascular Pharmacology, 56: 1-8, 2002.
- Nayeem, M.A Ethanol induced delayed cellular protection in mouse cardiac myocytes: role of inducible nitric oxide synthase. Polish Journal Pharmacology 55(4):595-602, 2003. Pubmed
- Nayeem, M.A., Matherne G.P and Mustafa S.J. Ischemic & pharmacological preconditioning further induces delayed cellular protection in A1AR over-expressed transgenic mice myocytes: role of A1AR, iNOS & KATP channels. Naunyn Schmiedebergs Archives Pharmacology, 367(3): 219-226, 2003. Pubmed
- Nayeem, M.A., and Mustafa S.J. Ischemic & pharmacological induction of delayed cellular protection in iNOS gene disrupted mice myocytes. Polish Journal Pharmacology, 55: 73-79, 2003. Pubmed
- Nayeem, M.A and Matherne, G.P. Pharmacological preconditioning induces additive tolerance in the form of ‘second window of protection’ in transgenic mouse cardiac myocytes over-expressing A1 adenosine receptors: role of A1 adenosine receptors and mitochondrial KATP channels. Circulation, 108 (18), 2003.
- Nayeem, M.A., Sub-lethal simulated ischemia promotes delayed resistance against sustained simulated ischemic injury via ATP-sensitive (K+) channels in murine myocytes: role of PKC & iNOS Antioxidant Redox Signaling, 6 (2):375-383, 2004. Pubmed
- Nayeem, M.A., Falck, J.R. Ledent, C. Ponnoth, D.S. Poloyac, S. M. Zeldin, D.C, Ansari, H.R and Mustafa, S.J. CYP epoxygenase-mediated relaxation in aorta through adenosine A2A receptor using A2A AR-/- and A2A AR+/+ mice. Am J Physiol Heart Circ Physiol. 2008 Nov;295(5):H2068-78.
- Nayeem, M.A., Ponnoth, D.S, Boegehold, M.A. Zeldin, D. C, Falck, J.R. and Mustafa, S.J. Adenosine A2A receptor mediated aortic relaxation in mice fed high salt diet: role of CYP epoxygenase. Am J Physiol Regul Integr Comp Physiol. 2009 Mar;296(3):R567-74.
- Nayeem, M.A., Zeldin, D.C. Boegehold, M.A. Morisseau, C. Marowsky, A. Ponnoth, D.S. Roush, K.P and Falck, J.R. Modulation by salt intake of the vascular response mediated through adenosine A2A receptor: role of CYP epoxygenase and soluble epoxide hydrolase. Am J Physiol Regul Integr Comp Physiol. 2010 Jul; 299(1):R325-333. Pubmed
- Nayeem, M.A., Zeldin, D.C. Boegehold, M.A and Falck, J.R. Salt modulates vascular response in eNOS-null mice through adenosine A2A receptor: role of cytochrome P450 2J2 and soluble epoxide hydrolase Mole Cell Biochem, 2010 Dec 14. [Epub ahead of print]. Pubmed
Book chapters Published:
- Kukreja, R.C., Nayeem, M.A., Qian, Y-Z, and Hess, M.L. Evolution and Adaptation of Free Radical Scavengers and the Potential for Therapeutic Intervention. In: B.K. Sharma et al., (eds), Adaptation Biology and Medicine, Vol. 1. Narosa Publishing House, New Delhi, 1997, 383- 398.
- Nayeem, M.A., Hess, M.L., Qian, Y.Z., Loesser, K.E., and Kukreja, R.C. Adaptation of Cultured Adult Rat Cardiac Myocytes Against Lethal Stresses: Role of Stress Proteins? In: B.K. Sharma et al., (eds), Adaptation Biology and Medicine, Vol. 2. Narosa Publishing House, New Delhi, 2000.
- Mustafa, S.J., Marala, R.B., Lust, R.M., and Nayeem, M.A. Ischemic Preconditioning Attenuates Protein Kinase C Mediated Increase in Coronary Vasoconstrictor Tone. In M. Fahim, (eds), Trends in Physiological Sciences cells to system, Vol. 1. Serials publications, New Delhi, 2002, 92-119.
Lab Personnel:
Brandy Wilmoth, Biology Technician
Isha Pradhan, Graduate Student
| |
|
|
 |
(L-R) Brandi Wilmoth, Biology Technician and Isha Pradhan, Graduate Student |
Dr. Mohammed Nayeem in the lab. |
| |
|
|
 |
| Isha Pradhan, Graduate Student, performs her duties in the lab. |
Brandi Wilmoth, Biology Technician, monitors an experiment. |
|
