Ayako Makino, PhD
Office Phone: 312-355-1018
Lab Phone: 312-996-3962
B.S., M.S., Ph.D.
Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan
Research Interest: Research interest in our laboratory centers on the modulation of endothelium function in pathological state. Vascular endothelial cells play critical roles in the vascular functions such as anticoagulant barrier between blood and vascular wall, regulation of vascular tone, and new vessel formation. In many cardiovascular diseases, endothelial cells are injured and/or dysfunctional, which leads to subsequent vascular complications. In our laboratory, we investigate cellular and molecular mechanisms of coronary vascular endothelial dysfunction in diabetes with the focus on vascular rarefaction and attenuated vascular relaxation.
Ongoing research projects in the lab:
1) GAP junction intercellular communication (GJIC) between endothelial cells
We demonstrated that coronary endothelial cells isolated from diabetic mice exhibit attenuated GJIC and decreased protein expression level of connexin 40 (one of the GAP junction components). We are currently investigating the upstream mechanisms that regulate connexin40 protein expression and the potential effect of connexin40 overexpression on vascular endothelial cell function in diabetic mice.
2) Ca2+ homeostasis in endothelial cells
Our previous study indicated that Ca2+ release from the endoplasmic reticulum in coronary endothelial cells is decreased in diabetic mice. Our current research is focused on defining the molecular mechanisms by which hyperglycemia regulates Ca2+ homeostasis in endothelial cells.
3) Mitochondrial morphology and physiology in endothelial cells
We recently show that 1) mitochondria in endothelial cells isolated from diabetic mice are more fragmented than in control endothelial cells, and 2) the fragmentation of mitochondria is induced by upregulation of Drp1 protein expression and excess production of superoxide. We now study the relationship between mitochondrial morphological changes and functions in diabetes.
In our lab, we use multiple preparations (e.g., freshly isolated endothelial cells, dissected vascular vessels, and a whole heart) and combined techniques (e.g., isometric tension measurement, electrophysiology, immunohistochemistry, fluorescence microscopy, and molecular biology) to study endothelium functions.
- Makino A, Skelton MM, Zou A-P, Roman R.J., and Cowley AW, Jr. Increased renal medullary oxidative stress produces hypertension. Hypertension. 39:667-672, 2002.
- Makino A, Skelton MM, Zou A-P, and Cowley AW, Jr. Increased renal medullary H2O2 leads to hypertension. Hypertension 42:25-30, 2003.
- Makino A, Glogauer M, Bokoch GM, Chien S, and Schmid-Schönbein GW. Control of neutrophil pseudopods by fluid shear: The role of Rho family GTPases. Am. J. Physiol. Cell Physiol. 288:863-871, 2005.
- Makino A, Prossnitz ER, Bünemann M, Wang JM, Yao W and Schmid-Schönbein GW. G protein-coupled receptors serve as mechanosensors for fluid shear stress in neutrophils. Am. J. Physiol. Cell Physiol. 290:1633-1639, 2006.
- Kamata K, Makino A, Kanie N, Oda S, Matsumoto T, Kobayashi T, Kikuchi T, Nishimura M and Honda T. Effects of anthocyanidin derivative (HK-008) on relaxation in rat perfused mesenterial bed. J. Smooth Muscle Res. 42:75-88, 2006.
- Makino A, Shin HY, Komai Y, Fukuda S, Coughlin M, Sugihara-Seki M and Schmid-Schönbein GW. Mechanotransduction in leukocyte activation. A review. Biorheology 44:221-249, 2007.
- Broderick KE, Alvarez L, Balasubramanian M, Belke DD, Makino A, Chan A, Woods VL Jr, Dillmann WH, Sharma VS, Pilz RB, Bigby T and Boss GR. Nitrosyl-cobinamide, a new and direct nitric oxide releasing drug effective in vivo. Exp. Biol. Med. 232:1432-1440, 2007.
- Xu M, Platoshyn O, Makino A, Dillmann WH. Akassoglou K, Remillard CV and Yuan JX. Characterization of agonist-induced vasoconstriction in mouse pulmonary artery. Am. J. Physiol. Heart Circ. Physiol. 294:H220-H228, 2008.
- Makino A, Platoshyn O, Suarez J, Yuan JX and Dillmann WH. Downregulation of connexin40 is associated with coronary endothelial cell dysfunction in streptozotocin-induced diabetic mice. Am. J. Physiol. Cell Physiol. 295:221-230. 2008.
- Xu M, Sachs B, Remillard CV, Makino A, Dillmann WH, Akassoglou K, and Yuan JX. p75 Neurotrophin receptor regulates agonist-induced pulmonary vasoconstriction. Am. J. Physiol. Heart Circ. Physiol. 295:H1529-H1538, 2008.
- Suarez J, Hu Y, Makino A, Fricovsky E, Wang H, and Dillmann WH. Alterations in mitochondrial function and cytosolic calcium induced by hyperglycemia are restored by mitochondrial transcription factor A in cardiomyocytes. Am. J. Physiol. Cell Physiol. 295:C1561-C1568, 2008.
- Makino A, Suarez J, Wang H, Belke DD, Scott B and Dillmann WH. Thyroid hormone receptor β is associated with coronary angiogenesis during pathological cardiac hypertrophy. Endocrinology 150:2008-2015, 2009.
- Li X, Zhang X, Leathers R, Makino A, Huang C, Parsa P, Marcias J, Yuan JX, Jamieson SW and Thistlethwaite PA. Notch3 signaling promotes the development of pulmonary arterial hypertension. Nat. Med. 15(11):1289-1297, 2009.
- Makino A, Scott BT, and Dillmann WH. Mitochondrial fragmentation and superoxide anion production in coronary endothelial cells from a mouse model of type 1 diabetes. Diabetologia 53(8):1783-1794, 2010.