The research activities in my laboratory have two major focuses. The one is to investigate the cellular and molecular mechanisms underlying the uterine vascular adaptation to pregnancy and chronic hypoxia. These studies are to test the hypothesis that chronic hypoxia during gestation causes maladaptation of steroid hormone receptor gene expression patterns in the uterine artery through enhanced promoter methylation resulting in heightened myogenic response of the uterine artery in pregnancy. The other area of research interests is to study fetal epigenetic programming of gene expression patterns caused by adverse intrauterine environments, which is essential in explaining many fundamental biological processes by which a variety of cardiovascular dysfunctions and disease emerge and evolve. We are interested in the assessments of molecular mechanisms of DNA methylation in epigenetic programming of gene expression patterns in the developing heart, and the role of sex and sex-defining steroids in determining an “ischemia-sensitive” phenotype in the heart.
1. Zhu R, Xiao D, Zhang L. Potassium channels and uterine vascular adaptation to pregnancy and chronic hypoxia. Curr Vasc Pharmacol Accepted for Publication.
2. Paradis A, Zhang L. Role of endothelin in uteroplacental circulation and fetal vascular function. Curr Vasc Pharmacol Accepted for Publication.
3. Xiong F, Zhang L. Role of hypothalamic-pituitary-adrenal axis in developmental programming of health and disease. Frontiers in Neuroendocrinology, Accepted for Publication.
4. Hu X, Zhang L. Function and regulation of large conductance Ca2+-activated K+ channel in vascular smooth muscle Cells. Drug Discovery Today 2012 Apr 13. [Epub ahead of print].
5. Li Y, Xiao D, Dasgupta C, Xiong F, Tong W, Yang S, Zhang L. Perinatal nicotine exposure increases vulnerability of hypoxic-ischemic brain injury in neonatal rats: role of angiotensin II receptors. Stroke 2012 Jun 26. [Epub ahead of print]
6. Dasgupta C, Xiao D, Xu Z, Yang S, Zhang L. Developmental nicotine exposure results in programming of alveolar simplification and interstitial pulmonary fibrosis in adult male rats. Reproduc Toxicol 2012 Jun 9. [Epub ahead of print].
7. Dasgupta C, Chen M, Zhang H, Yang S, Zhang L. Chronic hypoxia during gestation causes epigenetic repression of ERa gene in ovine uterine arteries via heightened promoter methylation. Hypertension, 60: 697-704, 2012.
8. Hu X, Xiao D, Zhu R, Huang X, Yang S, Wilson S, Zhang L. Chronic hypoxia suppresses pregnancy-induced upregulation of large conductance Ca2+-activated K+ channel activity in uterine arteries. Hypertension 60: 214-222, 2012.
9. Li Y, Gonzale P, Zhang L. Fetal stress and programming of hypoxic/ischemic-sensitive phenotype in the neonatal brain: mechanisms and possible interventions. Progress in Neurobiology 98: 145-165, 2012.
10. Xiong F, Xiao D, Zhang L. Norepinephrine causes epigenetic repression of PKCε gene in rodent hearts by activating Nox1-dependent reactive oxygen species production. FASEB J 26: 2753-2763, 2012.
11. Patterson AJ, Xiao D, Xiong F, Dixon B, Zhang L. Hypoxia-derived oxidative stress mediates epigenetic repression of PKCε gene in foetal rat hearts. Cardiovas Res 93: 302-310, 2012.
12. Shi L, Mao C, Zeng F, Zhang L, Xu Z. Central angiotensin I increases fetal swallowing activity and oxytocin release in near-term ovine fetus. Neuroendocrinology 95: 248-256, 2012.
13. Tong W, Zhang L. Hypoxia and fetal programming of matrix metalloproteinases. Drug Discovery Today invited keynote review, 17: 124-134, 2012.
14. Chen M, Zhang L. Epigenetic mechanisms in fetal programming of adult disease. Drug Discovery Today invited keynote review, 16: 1007-1018, 2011.
15. Tong W, Xue Q, Li Y, Zhang L. Maternal hypoxia alters matrix metalloproteinase expression patterns and causes cardiac remodeling in fetal and neonatal rats. Am J Physiol Heart Circ Physiol 301: H2113-2121, 2011.
16. Hu X, Xiao D, Zhu R, Huang X, Yang S, Wilson S, Zhang L. Pregnancy upregulates large-conductance Ca2+-activated K+ channel activity and attenuates myogenic tone in uterine arteries. Hypertension 58: 1132-1139, 2011.
17. Xiao D, Huang, X, Yang S, Zhang L. Antenatal nicotine induces heightened oxidative stress and vascular dysfunction in rat offspring. Br J Pharmacol 164: 1400-1409, 2011.
18. Zhang H, Fan Y, Xia F, Geng C, Mao C, Jiang S, He R, Zhang L, Xu Z. Prenatal water deprivation alters brain angiotensin system and dipsogenic changes in the offspring. Brain Res 1382: 128-36, 2011.
20. Dasgupta C, Zhang L. Angiotensin II receptors and drug discovery in cardiovascular disease. Drug Discovery Today invited keynote review, 16: 22-34, 2011.
21. Xue Q, Dasgupta C, Chen M, Zhang L. Fetal hypoxia causes programming of AT2R and cardiac vulnerability to ischemic injury in rat offspring. Cardiovas Res 89: 300-308, 2011.
22. Lawrence J, Chen M, Xiong F, Xiao D, Zhang H, Buchholz JN, Zhang L. Fetal nicotine exposure causes PKCe gene repression by promoter methylation in the heart. Cardiovas Res 89: 89-97, 2011.
23. Xiao D, Huang X, Yang S, Longo LD, Zhang L. Pregnancy downregulates actin polymerization and pressure-dependent myogenic tone in ovine uterine arteries. Hypertension 56: 1009-1015, 2010.
24. Xu F, Mao C, Ding Y, Rui C, Wu L, Shi A, Zhang L, Xu Z. Molecular and enzymatic profiles of mammalian DNA methyltransferases: structures and targets for drugs. Current Medicinal Chemistry 17: 4052-4071, 2010.
25. Xiao D, Longo LD, Zhang L. High altitude long-term hypoxic effect on KATP and L-type Ca2+ channel activities in uterine arteries of nonpregnant and pregnant sheep. Am J Obstet Gynecol 203:596.e6-596.e12, 2010.
26. Goyal R, Mittal A, Chu N, Arthur RA, Zhang L, Longo LD. Maturation and long term hypoxia-induced acclimatization responses in PKC-mediated signaling pathways in ovine cerebral arterial contractility. Am J Physiol Regul Integr Comp Physiol 299: R1377-R1386, 2010.
27. Charles SM, Zhang L, Cipolla MJ, Buchholz JN, Pearce WJ. Roles of cytosolic Ca2+ concentration and myofilament Ca2+ sensitization in age-dependent cerebrovascular myogenic tone. Am J Physiol Heart Circ Physiol 299: H1034-H1044, 2010.
28. Monau TR, Vargas VE, Zhang L, Myers DA, Ducsay CA. Nitric oxide inhibits ACTH-induced cortisol production in near term, long-term hypoxic ovine fetal adrenocortical cells. Reprod Sci 17: 955-962, 2010.
29. Chang K, Xiao D, Huang X, Xu Z, Yang S, Longo LD, Zhang L. Chronic hypoxia inhibits sex steroid hormone-mediated attenuation of ovine uterine arterial myogenic tone in pregnancy. Hypertension 56: 750-757, 2010.
30. Patterson AJ, Chen M, Xue Q, Xiao D, Zhang L. Chronic hypoxia induces epigenetic programming of PKCe gene repression in fetal rat heart. Circ Res 107: 365-373, 2010.
31. Patterson A, Zhang L. Hypoxia and fetal heart development. Current Molecular Medicine, Invited Review, 10: 653-666, 2010.
32. Xiao D, Huang X, Longo LD, Zhang L. PKC regulates a1-adrenoceptor-mediated contractions and baseline Ca2+ sensitivity in the uterine arteries of nonpregnant and pregnant sheep acclimatized to high altitude hypoxia. High Altitude Med Biol 11: 153-162, 2010.
33. Goyal R, Mittal A, Chu N, Zhang L, Longo LD. Alpha1-adrenergic receptor subtype function in fetal and adult cerebral arteries. Am J Physiol Heart Circ Physiol 298: H1797-H1806, 2010.
34. Tong W, Chen W, Ostrowski RP, Ma Q, Souvenir R, Zhang L, Zhang JH, Tang J. Maternal hypoxia increases the activity of MMPs and decreases the expression of TIMPs in the brain of neonatal rats. Dev Neurobiol 70: 182-94, 2010.
35. Shi L, Mao C, Xu Z, Zhang L. Angiotensin converting enzymes and drug discovery in cardiovascular diseases. Drug Discovery Today 15: 332-341, 2010.
36. Geng C, Mao C, Wu L, Cheng Y, Liu R, Chen B, Chen L, Zhang L, Xu Z. Cholinergic signal activated renin angiotensin system associated with cardiovascular changes in the ovine fetus. J Perinat Med 38: 71-76, 2010
37. Mao C, Ding Y, Zhou, Zhang H, Xu Z, Zhang L. Changes of renal AT1/AT2 receptors and structures in ovine fetuses following exposure to long-term hypoxia. Am J Nephrol, 31: 141-150, 2010.