Ayako Makino

Ayako Makino,

Associate Professor

Department: SR-CISSM-MAKINO LAB
Business Phone: (561) 228-2442
Business Email: ay.makino@ufl.edu

Research Profile

Our research focus centers on the modulation of endothelium function in pathological states and the pathogenic mechanisms involved in the development and progression of coronary and pulmonary vascular diseases in diabetes and pulmonary hypertension.

Vascular endothelial cells play critical roles in vascular functions such as regulation of vascular tone, new vessel formation, and anticoagulant barrier between blood and vascular wall. In many cardiovascular diseases, endothelial cells are injured and/or dysfunctional, leading to subsequent vascular complications. We investigate cellular and molecular mechanisms of endothelial dysfunction in diabetes and pulmonary hypertension, in particular cell-cell communication in endothelial cells and pericytes, calcium handling in the endoplasmic reticulum and mitochondria, and post-transcriptional regulation of genes related to endothelial dysfunction.

In my lab, we use multiple in vitro preparations (e.g., freshly isolated endothelial cells and small arteries from mouse and human hearts and lungs), in vivo preclinical animal models (e.g., genetically modified transgenic mice, experimental diabetic and pulmonary hypertension mouse/rat models), and combined techniques (e.g., cardiac hemodynamic assessment, isometric tension measurement, electrophysiology, immunohistochemistry, fluorescence microscopy, high-resolution microscopy, molecular biology, and bioinformatics) to study pathogenic mechanisms of coronary and pulmonary vascular disease.

Open Researcher and Contributor ID (ORCID)

0000-0003-1259-8604

Publications

2023
Pathophysiology and pathogenic mechanisms of pulmonary hypertension: role of membrane receptors, ion channels, and Ca2+ signaling.
Physiological reviews. 103(3):1827-1897 [DOI] 10.1152/physrev.00030.2021. [PMID] 36422993.
2023
Restoration of coronary microvascular function by OGA overexpression in a high-fat diet with low-dose streptozotocin-induced type 2 diabetic mice.
Diabetes & vascular disease research. 20(3) [DOI] 10.1177/14791641231173630. [PMID] 37186669.
2022
Efferocytosis of vascular cells in cardiovascular disease.
Pharmacology & therapeutics. 229 [DOI] 10.1016/j.pharmthera.2021.107919. [PMID] 34171333.
2022
Flavored and Nicotine-Containing E-Cigarettes Induce Impaired Angiogenesis and Diabetic Wound Healing via Increased Endothelial Oxidative Stress and Reduced NO Bioavailability.
Antioxidants (Basel, Switzerland). 11(5) [DOI] 10.3390/antiox11050904. [PMID] 35624768.
2022
In Vivo and Ex Vivo Experimental Approach for Studying Functional Role of Notch in Pulmonary Vascular Disease.
Methods in molecular biology (Clifton, N.J.). 2472:209-220 [DOI] 10.1007/978-1-0716-2201-8_17. [PMID] 35674903.
2022
Mechanosensitive cation currents through TRPC6 and Piezo1 channels in human pulmonary arterial endothelial cells.
American journal of physiology. Cell physiology. 323(4):C959-C973 [DOI] 10.1152/ajpcell.00313.2022. [PMID] 35968892.
2022
Mechanosensitive channel Piezo1 is required for pulmonary artery smooth muscle cell proliferation.
American journal of physiology. Lung cellular and molecular physiology. 322(5):L737-L760 [DOI] 10.1152/ajplung.00447.2021. [PMID] 35318857.
2021
Endothelial eNAMPT drives EndMT and preclinical PH: rescue by an eNAMPT-neutralizing mAb.
Pulmonary circulation. 11(4) [DOI] 10.1177/20458940211059712. [PMID] 34790349.
2021
Endothelial upregulation of mechanosensitive channel Piezo1 in pulmonary hypertension.
American journal of physiology. Cell physiology. 321(6):C1010-C1027 [DOI] 10.1152/ajpcell.00147.2021. [PMID] 34669509.
2021
Halofuginone, a promising drug for treatment of pulmonary hypertension.
British journal of pharmacology. 178(17):3373-3394 [DOI] 10.1111/bph.15442. [PMID] 33694155.
2021
HuR/Cx40 downregulation causes coronary microvascular dysfunction in type 2 diabetes.
JCI insight. 6(21) [DOI] 10.1172/jci.insight.147982. [PMID] 34747371.
2021
Mouse model of experimental pulmonary hypertension: Lung angiogram and right heart catheterization.
Pulmonary circulation. 11(4) [DOI] 10.1177/20458940211041512. [PMID] 34531976.
2021
mTOR Signaling in Pulmonary Vascular Disease: Pathogenic Role and Therapeutic Target.
International journal of molecular sciences. 22(4) [DOI] 10.3390/ijms22042144. [PMID] 33670032.
2021
TRPC6, a therapeutic target for pulmonary hypertension.
American journal of physiology. Lung cellular and molecular physiology. 321(6):L1161-L1182 [DOI] 10.1152/ajplung.00159.2021. [PMID] 34704831.
2021
Upregulation of Calcium Homeostasis Modulators in Contractile-To-Proliferative Phenotypical Transition of Pulmonary Arterial Smooth Muscle Cells.
Frontiers in physiology. 12 [DOI] 10.3389/fphys.2021.714785. [PMID] 34408668.
2021
Upregulation of Piezo1 (Piezo Type Mechanosensitive Ion Channel Component 1) Enhances the Intracellular Free Calcium in Pulmonary Arterial Smooth Muscle Cells From Idiopathic Pulmonary Arterial Hypertension Patients.
Hypertension (Dallas, Tex. : 1979). 77(6):1974-1989 [DOI] 10.1161/HYPERTENSIONAHA.120.16629. [PMID] 33813851.
2020
Altered Airway Microbiota Composition in Patients With Pulmonary Hypertension.
Hypertension (Dallas, Tex. : 1979). 76(5):1589-1599 [DOI] 10.1161/HYPERTENSIONAHA.120.15025. [PMID] 32921193.
2020
Chloroquine differentially modulates coronary vasodilation in control and diabetic mice.
British journal of pharmacology. 177(2):314-327 [DOI] 10.1111/bph.14864. [PMID] 31503328.
2020
Chronic Hypoxia Decreases Endothelial Connexin 40, Attenuates Endothelium-Dependent Hyperpolarization-Mediated Relaxation in Small Distal Pulmonary Arteries, and Leads to Pulmonary Hypertension.
Journal of the American Heart Association. 9(24) [DOI] 10.1161/JAHA.120.018327. [PMID] 33307937.
2020
Endothelial platelet-derived growth factor-mediated activation of smooth muscle platelet-derived growth factor receptors in pulmonary arterial hypertension.
Pulmonary circulation. 10(3) [DOI] 10.1177/2045894020948470. [PMID] 33294172.
2020
MicroRNA-mediated downregulation of K+ channels in pulmonary arterial hypertension.
American journal of physiology. Lung cellular and molecular physiology. 318(1):L10-L26 [DOI] 10.1152/ajplung.00010.2019. [PMID] 31553627.
2020
Notch enhances Ca2+ entry by activating calcium-sensing receptors and inhibiting voltage-gated K+ channels.
American journal of physiology. Cell physiology. 318(5):C954-C968 [DOI] 10.1152/ajpcell.00487.2019. [PMID] 32186932.
2020
Overexpression of p53 due to excess protein O-GlcNAcylation is associated with coronary microvascular disease in type 2 diabetes.
Cardiovascular research. 116(6):1186-1198 [DOI] 10.1093/cvr/cvz216. [PMID] 31504245.
2020
Pulmonary vessel casting in a rat model of monocrotaline-mediated pulmonary hypertension.
Pulmonary circulation. 10(3) [DOI] 10.1177/2045894020922129. [PMID] 32922742.
2020
Revisiting the mechanism of hypoxic pulmonary vasoconstriction using isolated perfused/ventilated mouse lung.
Pulmonary circulation. 10(4) [DOI] 10.1177/2045894020956592. [PMID] 33282184.
2020
Tetramethylpyrazine: A promising drug for the treatment of pulmonary hypertension.
British journal of pharmacology. 177(12):2743-2764 [DOI] 10.1111/bph.15000. [PMID] 31976548.
2020
Transcriptomic profiles in pulmonary arterial hypertension associate with disease severity and identify novel candidate genes.
Pulmonary circulation. 10(4) [DOI] 10.1177/2045894020968531. [PMID] 33343881.
2019
Aortic pathology from protein kinase G activation is prevented by an antioxidant vitamin B12 analog.
Nature communications. 10(1) [DOI] 10.1038/s41467-019-11389-1. [PMID] 31387997.
2019
Divergent changes of p53 in pulmonary arterial endothelial and smooth muscle cells involved in the development of pulmonary hypertension.
American journal of physiology. Lung cellular and molecular physiology. 316(1):L216-L228 [DOI] 10.1152/ajplung.00538.2017. [PMID] 30358436.
2019
Pulmonary vascular dysfunction in metabolic syndrome.
The Journal of physiology. 597(4):1121-1141 [DOI] 10.1113/JP275856. [PMID] 30125956.
2018
Akt2 (Protein Kinase B Beta) Stabilizes ATP7A, a Copper Transporter for Extracellular Superoxide Dismutase, in Vascular Smooth Muscle: Novel Mechanism to Limit Endothelial Dysfunction in Type 2 Diabetes Mellitus.
Arteriosclerosis, thrombosis, and vascular biology. 38(3):529-541 [DOI] 10.1161/ATVBAHA.117.309819. [PMID] 29301787.
2018
Diabetes Mellitus Associates with Increased Right Ventricular Afterload and Remodeling in Pulmonary Arterial Hypertension.
The American journal of medicine. 131(6):702.e7-702.e13 [DOI] 10.1016/j.amjmed.2017.12.046. [PMID] 29421689.
2018
Endothelial HIF-2α contributes to severe pulmonary hypertension due to endothelial-to-mesenchymal transition.
American journal of physiology. Lung cellular and molecular physiology. 314(2):L256-L275 [DOI] 10.1152/ajplung.00096.2017. [PMID] 29074488.
2018
Hypoxia selectively upregulates cation channels and increases cytosolic [Ca2+] in pulmonary, but not coronary, arterial smooth muscle cells.
American journal of physiology. Cell physiology. 314(4):C504-C517 [DOI] 10.1152/ajpcell.00272.2017. [PMID] 29351410.
2018
Overexpression of hexokinase 2 reduces mitochondrial calcium overload in coronary endothelial cells of type 2 diabetic mice.
American journal of physiology. Cell physiology. 314(6):C732-C740 [DOI] 10.1152/ajpcell.00350.2017. [PMID] 29513568.
2018
Pathogenic Role of mTORC1 and mTORC2 in Pulmonary Hypertension.
JACC. Basic to translational science. 3(6):744-762 [DOI] 10.1016/j.jacbts.2018.08.009. [PMID] 30623134.
2018
STIM2 (Stromal Interaction Molecule 2)-Mediated Increase in Resting Cytosolic Free Ca2+ Concentration Stimulates PASMC Proliferation in Pulmonary Arterial Hypertension.
Hypertension (Dallas, Tex. : 1979). 71(3):518-529 [DOI] 10.1161/HYPERTENSIONAHA.117.10503. [PMID] 29358461.
2017
Capsaicin-induced Ca2+ signaling is enhanced via upregulated TRPV1 channels in pulmonary artery smooth muscle cells from patients with idiopathic PAH.
American journal of physiology. Lung cellular and molecular physiology. 312(3):L309-L325 [DOI] 10.1152/ajplung.00357.2016. [PMID] 27979859.
2017
Chloroquine is a potent pulmonary vasodilator that attenuates hypoxia-induced pulmonary hypertension.
British journal of pharmacology. 174(22):4155-4172 [DOI] 10.1111/bph.13990. [PMID] 28849593.
2017
Hypoxia-induced pulmonary hypertension in type 2 diabetic mice.
Pulmonary circulation. 7(1):175-185 [DOI] 10.1086/690206. [PMID] 28680577.
2017
Mitochondrial connexin40 regulates mitochondrial calcium uptake in coronary endothelial cells.
American journal of physiology. Cell physiology. 312(4):C398-C406 [DOI] 10.1152/ajpcell.00283.2016. [PMID] 28122731.
2016
ATP promotes cell survival via regulation of cytosolic [Ca2+] and Bcl-2/Bax ratio in lung cancer cells.
American journal of physiology. Cell physiology. 310(2):C99-114 [DOI] 10.1152/ajpcell.00092.2015. [PMID] 26491047.
2016
Calcium-Sensing Receptor Regulates Cytosolic [Ca 2+ ] and Plays a Major Role in the Development of Pulmonary Hypertension.
Frontiers in physiology. 7 [PMID] 27867361.
2016
Isolation of Mouse Coronary Endothelial Cells.
Journal of visualized experiments : JoVE. (113) [DOI] 10.3791/53985. [PMID] 27404385.
2016
Pathogenic role of calcium-sensing receptors in the development and progression of pulmonary hypertension.
American journal of physiology. Lung cellular and molecular physiology. 310(9):L846-59 [DOI] 10.1152/ajplung.00050.2016. [PMID] 26968768.
2015
Deficiency of Akt1, but not Akt2, attenuates the development of pulmonary hypertension.
American journal of physiology. Lung cellular and molecular physiology. 308(2):L208-20 [DOI] 10.1152/ajplung.00242.2014. [PMID] 25416384.
2015
Notch Activation of Ca(2+) Signaling in the Development of Hypoxic Pulmonary Vasoconstriction and Pulmonary Hypertension.
American journal of respiratory cell and molecular biology. 53(3):355-67 [DOI] 10.1165/rcmb.2014-0235OC. [PMID] 25569851.
2015
O-GlcNAcase overexpression reverses coronary endothelial cell dysfunction in type 1 diabetic mice.
American journal of physiology. Cell physiology. 309(9):C593-9 [DOI] 10.1152/ajpcell.00069.2015. [PMID] 26269457.
2015
SGLT inhibitors attenuate NO-dependent vascular relaxation in the pulmonary artery but not in the coronary artery.
American journal of physiology. Lung cellular and molecular physiology. 309(9):L1027-36 [DOI] 10.1152/ajplung.00167.2015. [PMID] 26361875.
2015
Upregulated expression of STIM2, TRPC6, and Orai2 contributes to the transition of pulmonary arterial smooth muscle cells from a contractile to proliferative phenotype.
American journal of physiology. Cell physiology. 308(8):C581-93 [DOI] 10.1152/ajpcell.00202.2014. [PMID] 25673771.
2014
Flow shear stress enhances intracellular Ca2+ signaling in pulmonary artery smooth muscle cells from patients with pulmonary arterial hypertension.
American journal of physiology. Cell physiology. 307(4):C373-83 [DOI] 10.1152/ajpcell.00115.2014. [PMID] 24920677.
2014
Hyperthermia generated with ferucarbotran (Resovist®) in an alternating magnetic field enhances cisplatin-induced apoptosis of cultured human oral cancer cells.
The journal of physiological sciences : JPS. 64(3):177-83 [DOI] 10.1007/s12576-014-0309-8. [PMID] 24619404.
2014
In vivo selective expression of thyroid hormone receptor α1 in endothelial cells attenuates myocardial injury in experimental myocardial infarction in mice.
American journal of physiology. Regulatory, integrative and comparative physiology. 307(3):R340-6 [DOI] 10.1152/ajpregu.00449.2013. [PMID] 24848360.
2014
Store-operated Ca2+ entry (SOCE) regulates melanoma proliferation and cell migration.
PloS one. 9(2) [DOI] 10.1371/journal.pone.0089292. [PMID] 24586666.
2013
Chronic hypoxia selectively enhances L- and T-type voltage-dependent Ca2+ channel activity in pulmonary artery by upregulating Cav1.2 and Cav3.2.
American journal of physiology. Lung cellular and molecular physiology. 305(2):L154-64 [DOI] 10.1152/ajplung.00313.2012. [PMID] 23686856.
2013
Coronary endothelial dysfunction and mitochondrial reactive oxygen species in type 2 diabetic mice.
American journal of physiology. Cell physiology. 305(10):C1033-40 [DOI] 10.1152/ajpcell.00234.2013. [PMID] 23986204.
2013
Dihydropyridine Ca(2+) channel blockers increase cytosolic [Ca(2+)] by activating Ca(2+)-sensing receptors in pulmonary arterial smooth muscle cells.
Circulation research. 112(4):640-50 [DOI] 10.1161/CIRCRESAHA.113.300897. [PMID] 23300272.
2013
Functional characterization of voltage-dependent Ca(2+) channels in mouse pulmonary arterial smooth muscle cells: divergent effect of ROS.
American journal of physiology. Cell physiology. 304(11):C1042-52 [DOI] 10.1152/ajpcell.00304.2012. [PMID] 23426966.
2012
Apolipoprotein E enhances endothelial-NO production by modulating caveolin 1 interaction with endothelial NO synthase.
Hypertension (Dallas, Tex. : 1979). 60(4):1040-6 [DOI] 10.1161/HYPERTENSIONAHA.112.196667. [PMID] 22914792.
2012
Enhanced Ca(2+)-sensing receptor function in idiopathic pulmonary arterial hypertension.
Circulation research. 111(4):469-81 [DOI] 10.1161/CIRCRESAHA.112.266361. [PMID] 22730443.
2012
Mitochondrial function in vascular endothelial cell in diabetes.
Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi. 48(1):1-26 [PMID] 22504486.
2012
STIM1 restores coronary endothelial function in type 1 diabetic mice.
Circulation research. 111(9):1166-75 [DOI] 10.1161/CIRCRESAHA.112.275743. [PMID] 22896585.
2012
The role of oxysterols in control of endothelial stiffness.
Journal of lipid research. 53(7):1348-58 [DOI] 10.1194/jlr.M027102. [PMID] 22496390.
2012
Thyroid hormone receptor-α and vascular function.
American journal of physiology. Cell physiology. 302(9):C1346-52 [DOI] 10.1152/ajpcell.00292.2011. [PMID] 22322976.
2012
VDAC: old protein with new roles in diabetes.
American journal of physiology. Cell physiology. 303(10):C1055-60 [DOI] 10.1152/ajpcell.00087.2012. [PMID] 22972802.
2011
Endothelial and smooth muscle cell ion channels in pulmonary vasoconstriction and vascular remodeling.
Comprehensive Physiology. 1(3):1555-602 [DOI] 10.1002/cphy.c100023. [PMID] 23733654.
2011
Fenfluramine-induced gene dysregulation in human pulmonary artery smooth muscle and endothelial cells.
Pulmonary circulation. 1(3):405-18 [DOI] 10.4103/2045-8932.87310. [PMID] 22140631.
2011
Regulation of mitochondrial morphology and function by O-GlcNAcylation in neonatal cardiac myocytes.
American journal of physiology. Regulatory, integrative and comparative physiology. 300(6):R1296-302 [DOI] 10.1152/ajpregu.00437.2010. [PMID] 21346246.
2011
Role of reactive oxygen species and redox in regulating the function of transient receptor potential channels.
Antioxidants & redox signaling. 15(6):1549-65 [DOI] 10.1089/ars.2010.3648. [PMID] 21126186.
2011
STIM2 Contributes to Enhanced Store-operated Ca Entry in Pulmonary Artery Smooth Muscle Cells from Patients with Idiopathic Pulmonary Arterial Hypertension.
Pulmonary circulation. 1(1):84-94 [PMID] 21709766.
2010
Tension Measurement in Isolated Rat and Mouse Pulmonary Artery.
Drug discovery today. Disease models. 7(3-4):123-130 [PMID] 23175638.
2009
Notch3 signaling promotes the development of pulmonary arterial hypertension.
Nature medicine. 15(11):1289-97 [DOI] 10.1038/nm.2021. [PMID] 19855400.
2009
Thyroid hormone receptor-beta is associated with coronary angiogenesis during pathological cardiac hypertrophy.
Endocrinology. 150(4):2008-15 [DOI] 10.1210/en.2008-0634. [PMID] 19074585.
2008
Alterations in mitochondrial function and cytosolic calcium induced by hyperglycemia are restored by mitochondrial transcription factor A in cardiomyocytes.
American journal of physiology. Cell physiology. 295(6):C1561-8 [DOI] 10.1152/ajpcell.00076.2008. [PMID] 19060297.
2008
Characterization of agonist-induced vasoconstriction in mouse pulmonary artery.
American journal of physiology. Heart and circulatory physiology. 294(1):H220-8 [PMID] 17982012.
2008
Downregulation of connexin40 is associated with coronary endothelial cell dysfunction in streptozotocin-induced diabetic mice.
American journal of physiology. Cell physiology. 295(1):C221-30 [DOI] 10.1152/ajpcell.00433.2007. [PMID] 18463230.
2008
p75 neurotrophin receptor regulates agonist-induced pulmonary vasoconstriction.
American journal of physiology. Heart and circulatory physiology. 295(4):H1529-38 [DOI] 10.1152/ajpheart.00115.2008. [PMID] 18689502.
2007
Mechanotransduction in leukocyte activation: a review.
Biorheology. 44(4):221-49 [PMID] 18094448.
2007
Nitrosyl-cobinamide, a new and direct nitric oxide releasing drug effective in vivo.
Experimental biology and medicine (Maywood, N.J.). 232(11):1432-40 [PMID] 18040067.
2006
Effects of anthocyanidin derivative (HK-008) on relaxation in rat perfused mesenterial bed.
Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi. 42(2-3):75-88 [PMID] 17001114.
2006
G protein-coupled receptors serve as mechanosensors for fluid shear stress in neutrophils.
American journal of physiology. Cell physiology. 290(6):C1633-9 [PMID] 16436471.
2005
Control of neutrophil pseudopods by fluid shear: role of Rho family GTPases.
American journal of physiology. Cell physiology. 288(4):C863-71 [PMID] 15561759.
2003
Increased renal medullary H2O2 leads to hypertension.
Hypertension (Dallas, Tex. : 1979). 42(1):25-30 [PMID] 12782642.
2002
Effects of chronic administration of L-arginine on vasoactive responses induced by endothelin-1 and its plasma level in streptozotocin-induced diabetic rats.
Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi. 38(4-5):101-15 [PMID] 12596889.
2002
Increased renal medullary oxidative stress produces hypertension.
Hypertension (Dallas, Tex. : 1979). 39(2 Pt 2):667-72 [PMID] 11882628.
2002
Structural studies on IgG oligosaccharides of patients with primary Sjögren’s syndrome.
Glycoconjugate journal. 19(1):23-31 [PMID] 12652077.

Contact Details

Phones:
Business:
(561) 228-2442
Emails:
Business:
ay.makino@ufl.edu
Addresses:
Business Mailing:
3B2
130 Scripps Way
Jupiter FL 33458
Business Street:
120 Scripps Way
Jupiter FL 33458