TY  - JOUR
AU  - Sun, Wen-Tao
AU  - Wang, Xiang-Chong
AU  - Novaković, Aleksandra
AU  - Wang, Jun
AU  - He, Guo-Wei
AU  - Yang, Qin
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3361
AB  - Objectives: We recently reported the involvement of ER stress-mediated BKCa channel inhibition in homocysteine-induced coronary dilator dysfunction. In another study, we demonstrated that tetramethylpyrazine (TMP), an active ingredient of the Chinese herb Chuanxiong, possesses potent anti-ER stress capacity. The present study investigated whether TMP protects BKCa channels from homocysteine-induced inhibition and whether suppression of ER stress is a mechanism contributing to the protection. Furthermore, we explored the signaling transduction involved in TMP-conferred protection on BKCa channels. Methods: BKCa channel-mediated relaxation was studied in porcine small coronary arteries. Expressions of BKCa channel subunits, ER stress molecules, and E3 ubiquitin ligases, as well as BKCa ubiquitination were determined in porcine coronary arterial smooth muscle cells (PCASMCs). Whole-cell BKCa currents were recorded. Results: Exposure of PCASMCs to homocysteine or the chemical ER stressor tunicamycin increased the expression of ER stress molecules, which was significantly inhibited by TMP. Suppression of ER stress by TMP preserved the BKCa beta 1 protein level and restored the BKCa current in PCASMCs, concomitant with an improved BKCa mediated dilatation in coronary arteries. TMP attenuated homocysteine-induced BKCa beta 1 protein ubiquitination, in which inhibition of ER stress-mediated FoxO3a activation and FoxO3a-dependent atrogin-1 and Murf-1 was involved. Conclusions: Reversal of BKCa channel inhibition via suppressing ER stress-mediated loss of beta 1 subunits contributes to the protective effect of TMP against homocysteine on coronary dilator function. Inhibition of FoxO3a-dependent ubiquitin ligases is involved in TMP-conferred normalization of BKCa beta 1 protein level. These results provide new mechanistic insights into the cardiovascular benefits of TMP.
PB  - Elsevier Science Inc, New York
T2  - Vibrational Spectroscopy
T1  - Protection of dilator function of coronary arteries from homocysteine by tetramethylpyrazine: Role of ER stress in modulation of BKCa channels
VL  - 113
SP  - 27
EP  - 37
DO  - 10.1016/j.vph.2018.10.009
ER  - 

@article{
author = "Sun, Wen-Tao and Wang, Xiang-Chong and Novaković, Aleksandra and Wang, Jun and He, Guo-Wei and Yang, Qin",
year = "2019",
abstract = "Objectives: We recently reported the involvement of ER stress-mediated BKCa channel inhibition in homocysteine-induced coronary dilator dysfunction. In another study, we demonstrated that tetramethylpyrazine (TMP), an active ingredient of the Chinese herb Chuanxiong, possesses potent anti-ER stress capacity. The present study investigated whether TMP protects BKCa channels from homocysteine-induced inhibition and whether suppression of ER stress is a mechanism contributing to the protection. Furthermore, we explored the signaling transduction involved in TMP-conferred protection on BKCa channels. Methods: BKCa channel-mediated relaxation was studied in porcine small coronary arteries. Expressions of BKCa channel subunits, ER stress molecules, and E3 ubiquitin ligases, as well as BKCa ubiquitination were determined in porcine coronary arterial smooth muscle cells (PCASMCs). Whole-cell BKCa currents were recorded. Results: Exposure of PCASMCs to homocysteine or the chemical ER stressor tunicamycin increased the expression of ER stress molecules, which was significantly inhibited by TMP. Suppression of ER stress by TMP preserved the BKCa beta 1 protein level and restored the BKCa current in PCASMCs, concomitant with an improved BKCa mediated dilatation in coronary arteries. TMP attenuated homocysteine-induced BKCa beta 1 protein ubiquitination, in which inhibition of ER stress-mediated FoxO3a activation and FoxO3a-dependent atrogin-1 and Murf-1 was involved. Conclusions: Reversal of BKCa channel inhibition via suppressing ER stress-mediated loss of beta 1 subunits contributes to the protective effect of TMP against homocysteine on coronary dilator function. Inhibition of FoxO3a-dependent ubiquitin ligases is involved in TMP-conferred normalization of BKCa beta 1 protein level. These results provide new mechanistic insights into the cardiovascular benefits of TMP.",
publisher = "Elsevier Science Inc, New York",
journal = "Vibrational Spectroscopy",
title = "Protection of dilator function of coronary arteries from homocysteine by tetramethylpyrazine: Role of ER stress in modulation of BKCa channels",
volume = "113",
pages = "27-37",
doi = "10.1016/j.vph.2018.10.009"
}

Sun, W., Wang, X., Novaković, A., Wang, J., He, G.,& Yang, Q.. (2019). Protection of dilator function of coronary arteries from homocysteine by tetramethylpyrazine: Role of ER stress in modulation of BKCa channels. in Vibrational Spectroscopy
Elsevier Science Inc, New York., 113, 27-37.
https://doi.org/10.1016/j.vph.2018.10.009

Sun W, Wang X, Novaković A, Wang J, He G, Yang Q. Protection of dilator function of coronary arteries from homocysteine by tetramethylpyrazine: Role of ER stress in modulation of BKCa channels. in Vibrational Spectroscopy. 2019;113:27-37.
doi:10.1016/j.vph.2018.10.009 .

Sun, Wen-Tao, Wang, Xiang-Chong, Novaković, Aleksandra, Wang, Jun, He, Guo-Wei, Yang, Qin, "Protection of dilator function of coronary arteries from homocysteine by tetramethylpyrazine: Role of ER stress in modulation of BKCa channels" in Vibrational Spectroscopy, 113 (2019):27-37,
https://doi.org/10.1016/j.vph.2018.10.009 . .

TY  - JOUR
AU  - Hou, Hai-Tao
AU  - Wang, Jun
AU  - Wang, Zheng-Qing
AU  - Liu, Xiao-Cheng
AU  - Marinko, Marija
AU  - Novaković, Aleksandra
AU  - Yang, Qin
AU  - He, Guo-Wei
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2525
AB  - Background. Graft spasm remains challenging in coronary artery bypass grafting (CABG). Calcium antagonists are commonly used in patients with coronary artery disease. This study investigated the inhibitory effect of third-generation dihydropyridine calcium channel antagonist benidipine on the vasoconstriction induced by various vasoconstrictors in the human internalmammary artery(IMA). Methods. Isolated human IMA rings (N = 65, taken from 37 patients undergoing CABG) were studied in a myograph in 2 ways: the relaxing effect of benidipine on vasoconstrictor-induced precontraction by KCl and U46619 and the depressing effect of benidipine at plasma concentrations on the contraction. Enzyme-linked immunosorbent assay (ELISA) was used to measure the change of the protein related to the L-type calcium channel. Results. Benidipine caused more relaxation in KCl-contracted (86.7% +/- 3.3%; n = 12) than in U46619-contracted (63.8% +/- 5.3%; n = 8; p  lt  0.001) IMA rings. Pretreatment of IMA with plasma concentrations of benidipine (-6.92 log M) significantly depressed subsequent contraction by KCl (from 17.3 +/- 2.7 mN to 7.4 +/- 1.2 mN; n = 6; p  lt  0.05) but did not significantly affect the contraction caused by U46619. Benidipine also caused a decrease of caveolin (CaV) 1.2 protein content (0.55 +/- 0.02 versus 0.63 +/- 0.02 mg/mL; p  lt  0.05). Conclusions. We conclude that in human IMA, the third-generation dihydropyridine calcium channel antagonist benidipine has a potent inhibitory effect on the vasoconstriction mediated by a variety of vasoconstrictors. Use of benidipine in patients undergoing CABG may provide vasorelaxant or antispastic effects in the grafts.
PB  - Elsevier Science Inc, New York
T2  - Annals of Thoracic Surgery
T1  - Effect of Benidipine in Human Internal Mammary Artery and Clinical Implications
VL  - 101
IS  - 5
SP  - 1789
EP  - 1795
DO  - 10.1016/j.athoracsur.2015.10.029
ER  - 

@article{
author = "Hou, Hai-Tao and Wang, Jun and Wang, Zheng-Qing and Liu, Xiao-Cheng and Marinko, Marija and Novaković, Aleksandra and Yang, Qin and He, Guo-Wei",
year = "2016",
abstract = "Background. Graft spasm remains challenging in coronary artery bypass grafting (CABG). Calcium antagonists are commonly used in patients with coronary artery disease. This study investigated the inhibitory effect of third-generation dihydropyridine calcium channel antagonist benidipine on the vasoconstriction induced by various vasoconstrictors in the human internalmammary artery(IMA). Methods. Isolated human IMA rings (N = 65, taken from 37 patients undergoing CABG) were studied in a myograph in 2 ways: the relaxing effect of benidipine on vasoconstrictor-induced precontraction by KCl and U46619 and the depressing effect of benidipine at plasma concentrations on the contraction. Enzyme-linked immunosorbent assay (ELISA) was used to measure the change of the protein related to the L-type calcium channel. Results. Benidipine caused more relaxation in KCl-contracted (86.7% +/- 3.3%; n = 12) than in U46619-contracted (63.8% +/- 5.3%; n = 8; p  lt  0.001) IMA rings. Pretreatment of IMA with plasma concentrations of benidipine (-6.92 log M) significantly depressed subsequent contraction by KCl (from 17.3 +/- 2.7 mN to 7.4 +/- 1.2 mN; n = 6; p  lt  0.05) but did not significantly affect the contraction caused by U46619. Benidipine also caused a decrease of caveolin (CaV) 1.2 protein content (0.55 +/- 0.02 versus 0.63 +/- 0.02 mg/mL; p  lt  0.05). Conclusions. We conclude that in human IMA, the third-generation dihydropyridine calcium channel antagonist benidipine has a potent inhibitory effect on the vasoconstriction mediated by a variety of vasoconstrictors. Use of benidipine in patients undergoing CABG may provide vasorelaxant or antispastic effects in the grafts.",
publisher = "Elsevier Science Inc, New York",
journal = "Annals of Thoracic Surgery",
title = "Effect of Benidipine in Human Internal Mammary Artery and Clinical Implications",
volume = "101",
number = "5",
pages = "1789-1795",
doi = "10.1016/j.athoracsur.2015.10.029"
}

Hou, H., Wang, J., Wang, Z., Liu, X., Marinko, M., Novaković, A., Yang, Q.,& He, G.. (2016). Effect of Benidipine in Human Internal Mammary Artery and Clinical Implications. in Annals of Thoracic Surgery
Elsevier Science Inc, New York., 101(5), 1789-1795.
https://doi.org/10.1016/j.athoracsur.2015.10.029

Hou H, Wang J, Wang Z, Liu X, Marinko M, Novaković A, Yang Q, He G. Effect of Benidipine in Human Internal Mammary Artery and Clinical Implications. in Annals of Thoracic Surgery. 2016;101(5):1789-1795.
doi:10.1016/j.athoracsur.2015.10.029 .

Hou, Hai-Tao, Wang, Jun, Wang, Zheng-Qing, Liu, Xiao-Cheng, Marinko, Marija, Novaković, Aleksandra, Yang, Qin, He, Guo-Wei, "Effect of Benidipine in Human Internal Mammary Artery and Clinical Implications" in Annals of Thoracic Surgery, 101, no. 5 (2016):1789-1795,
https://doi.org/10.1016/j.athoracsur.2015.10.029 . .