Hydrogen sulfide and nitric oxide are mutually dependent in the regulation of angiogenesis and endothelium-dependent vasorelaxation

被引:565
作者
Coletta, Ciro [1 ,2 ]
Papapetropoulos, Andreas [1 ,2 ,3 ]
Erdelyi, Katalin [1 ,2 ]
Olah, Gabor [1 ,2 ]
Modis, Katalin [1 ,2 ]
Panopoulos, Panagiotis [3 ]
Asimakopoulou, Antonia [3 ]
Geroe, Domokos [1 ,2 ]
Sharina, Iraida [4 ]
Martin, Emil [4 ]
Szabo, Csaba [1 ,2 ]
机构
[1] Univ Texas Med Branch, Dept Anesthesiol, Galveston, TX 77555 USA
[2] Shriners Burns Hosp Children, Galveston, TX 77555 USA
[3] Univ Patras, Dept Pharm, Mol Pharmacol Lab, Patras 26504, Greece
[4] Univ Texas Med Sch Houston, Dept Internal Med, Div Cardiol, Houston, TX 77030 USA
基金
美国国家卫生研究院;
关键词
SOLUBLE GUANYLYL CYCLASE; GROWTH-FACTOR; H2S; MOLECULE; TARGETS; MODEL;
D O I
10.1073/pnas.1202916109
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Hydrogen sulfide (H2S) is a unique gasotransmitter, with regulatory roles in the cardiovascular, nervous, and immune systems. Some of the vascular actions of H2S (stimulation of angiogenesis, relaxation of vascular smooth muscle) resemble those of nitric oxide (NO). Although it was generally assumed that H2S and NO exert their effects via separate pathways, the results of the current study show that H2S and NO are mutually required to elicit angiogenesis and vasodilatation. Exposure of endothelial cells to H2S increases intracellular cyclic guanosine 5'-monophosphate (cGMP) in a NO-dependent manner, and activated protein kinase G (PKG) and its downstream effector, the vasodilator-stimulated phosphoprotein (VASP). Inhibition of endothelial isoform of NO synthase (eNOS) or PKG-I abolishes the H2S-stimulated angiogenic response, and attenuated H2S-stimulated vasorelaxation, demonstrating the requirement of NO in vascular H2S signaling. Conversely, silencing of the H2S-producing enzyme cystathionine-gamma-lyase abolishes NO-stimulated cGMP accumulation and angiogenesis and attenuates the acetylcholine-induced vasorelaxation, indicating a partial requirement of H2S in the vascular activity of NO. The actions of H2S and NO converge at cGMP; though H2S does not directly activate soluble guanylyl cyclase, it maintains a tonic inhibitory effect on PDE5, thereby delaying the degradation of cGMP. H2S also activates PI3K/Akt, and increases eNOS phosphorylation at its activating site S1177. The cooperative action of the two gasotransmitters on increasing and maintaining intracellular cGMP is essential for PKG activation and angiogenesis and vasorelaxation. H2S-induced wound healing and microvessel growth in matrigel plugs is suppressed by pharmacological inhibition or genetic ablation of eNOS. Thus, NO and H2S are mutually required for the physiological control of vascular function.
引用
收藏
页码:9161 / 9166
页数:6
相关论文
共 41 条
  • [21] H2S Signals Through Protein S-Sulfhydration
    Mustafa, Asif K.
    Gadalla, Moataz M.
    Sen, Nilkantha
    Kim, Seyun
    Mu, Weitong
    Gazi, Sadia K.
    Barrow, Roxanne K.
    Yang, Guangdong
    Wang, Rui
    Snyder, Solomon H.
    [J]. SCIENCE SIGNALING, 2009, 2 (96) : ra72
  • [22] Signaling by Gasotransmitters
    Mustafa, Asif K.
    Gadalla, Moataz M.
    Snyder, Solomon H.
    [J]. SCIENCE SIGNALING, 2009, 2 (68) : re2
  • [23] The aortic ring model of angiogenesis: a quarter century of search and discovery
    Nicosia, R. F.
    [J]. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2009, 13 (10): : 4113 - 4136
  • [24] Effect of Hydrogen Sulfide in a Porcine Model of Myocardial Ischemia-Reperfusion: Comparison of Different Administration Regimens and Characterization of the Cellular Mechanisms of Protection
    Osipov, Robert M.
    Robich, Michael P.
    Feng, Jun
    Liu, Yuhong
    Clements, Richard T.
    Glazer, Hilary P.
    Sodha, Neel R.
    Szabo, Csaba
    Bianchi, Cesario
    Sellke, Frank W.
    [J]. JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 2009, 54 (04) : 287 - 297
  • [25] Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells
    Papapetropoulos, A
    García-Cardeña, G
    Madri, JA
    Sessa, WC
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (12) : 3131 - 3139
  • [26] Hydrogen sulfide is an endogenous stimulator of angiogenesis
    Papapetropoulos, Andreas
    Pyriochou, Anastasia
    Altaany, Zaid
    Yang, Guangdong
    Marazioti, Antonia
    Zhou, Zongmin
    Jeschke, Mark G.
    Branski, Ludwik K.
    Herndon, David N.
    Wang, Rui
    Szabo, Csaba
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (51) : 21972 - 21977
  • [27] cGMP-dependent and -independent properties of nitric angiogenesis-related oxide
    Pyriochou, Anastasia
    Vassilakopoulos, Theodoros
    Zhou, Zongmin
    Papapetropoulos, Andreas
    [J]. LIFE SCIENCES, 2007, 81 (21-22) : 1549 - 1554
  • [28] Soluble guanylyl cyclase activation promotes angiogenesis
    Pyriochou, Anastasia
    Beis, Dimitris
    Koika, Vasiliki
    Potytarchou, Christos
    Papadimitriou, Evangelia
    Zhou, Zongmin
    Papapetropoulos, Andreas
    [J]. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2006, 319 (02) : 663 - 671
  • [29] Ramli J, 2011, CARDIOL J, V18, P352
  • [30] Hydrogen sulfide replacement therapy protects the vascular endothelium in hyperglycemia by preserving mitochondrial function
    Suzuki, Kunihiro
    Olah, Gabor
    Modis, Katalin
    Coletta, Ciro
    Kulp, Gabriella
    Geroe, Domokos
    Szoleczky, Petra
    Chang, Tuanjie
    Zhou, Zongmin
    Wu, Lingyun
    Wang, Rui
    Papapetropoulos, Andreas
    Szabo, Csaba
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (33) : 13829 - 13834