Display options
Cite
Juguilon C, Wang Z, Wang Y, et al. Mechanism of the switch from NO to H. Basic Res Cardiol. 2022;117(1):2doi: 10.1007/s00395-022-00910-1.
Juguilon, C., Wang, Z., Wang, Y., Enrick, M., Jamaiyar, A., Xu, Y., Gadd, J., Chen, C. W., Pu, A., Kolz, C., Ohanyan, V., Chen, Y. R., Hardwick, J., Zhang, Y., Chilian, W. M., & Yin, L. (2022). Mechanism of the switch from NO to H. Basic research in cardiology, 117(1), 2. https://doi.org/10.1007/s00395-022-00910-1
Juguilon, Cody, et al. "Mechanism of the switch from NO to H." Basic research in cardiology vol. 117,1 (2022): 2. doi: https://doi.org/10.1007/s00395-022-00910-1
Juguilon C, Wang Z, Wang Y, Enrick M, Jamaiyar A, Xu Y, Gadd J, Chen CW, Pu A, Kolz C, Ohanyan V, Chen YR, Hardwick J, Zhang Y, Chilian WM, Yin L. Mechanism of the switch from NO to H. Basic Res Cardiol. 2022 Jan 13;117(1):2. doi: 10.1007/s00395-022-00910-1. PMID: 35024970.
Copy Download .nbib Format: NLM
Share it on

Basic Res Cardiol. 2022 Jan 13;117(1):2. doi: 10.1007/s00395-022-00910-1.

Mechanism of the switch from NO to H.

Basic research in cardiology

Cody Juguilon, Zhiyuan Wang, Yang Wang, Molly Enrick, Anurag Jamaiyar, Yanyong Xu, James Gadd, Chwen-Lih W Chen, Autumn Pu, Chris Kolz, Vahagn Ohanyan, Yeong-Renn Chen, James Hardwick, Yanqiao Zhang, William M Chilian, Liya Yin

Affiliations

  1. Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH, 44272, USA.
  2. Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH, 44272, USA. [email protected].

PMID: 35024970 DOI: 10.1007/s00395-022-00910-1

Abstract

Coronary microvascular dysfunction is prevalent among people with diabetes and is correlated with cardiac mortality. Compromised endothelial-dependent dilation (EDD) is an early event in the progression of diabetes, but its mechanisms remain incompletely understood. Nitric oxide (NO) is the major endothelium-dependent vasodilatory metabolite in the healthy coronary circulation, but this switches to hydrogen peroxide (H

© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.

Keywords: Coronary circulation; Coronary dilation; Diabetes; Endothelial dysfunction; Microvascular dysfunction

References

  1. Allaqaband H, Gutterman DD, Kadlec AO (2018) Physiological consequences of coronary arteriolar dysfunction and its influence on cardiovascular disease. Physiology (Bethesda) 33:338–347. https://doi.org/10.1152/physiol.00019.2018 - PubMed
  2. Andes LJ, Cheng YJ, Rolka DB, Gregg EW, Imperatore G (2020) Prevalence of prediabetes among adolescents and young adults in the United States, 2005–2016. JAMA Pediatr 174:e194498. https://doi.org/10.1001/jamapediatrics.2019.4498 - PubMed
  3. Aronson D, Edelman ER (2014) Coronary artery disease and diabetes mellitus. Cardiol Clin 32:439–455. https://doi.org/10.1016/j.ccl.2014.04.001 - PubMed
  4. Bagi Z, Koller A, Kaley G (2003) Superoxide-NO interaction decreases flow- and agonist-induced dilations of coronary arterioles in Type 2 diabetes mellitus. Am J Physiol Heart Circ Physiol 285:H1404-1410. https://doi.org/10.1152/ajpheart.00235.2003 - PubMed
  5. Ben-Nun D, Buja LM, Fuentes F (2020) Prevention of heart failure with preserved ejection fraction (HFpEF): reexamining microRNA-21 inhibition in the era of oligonucleotide-based therapeutics. Cardiovasc Pathol 49:107243. https://doi.org/10.1016/j.carpath.2020.107243 - PubMed
  6. Beyer AM, Freed JK, Durand MJ, Riedel M, Ait-Aissa K, Green P, Hockenberry JC, Morgan RG, Donato AJ, Peleg R, Gasparri M, Rokkas CK, Santos JH, Priel E, Gutterman DD (2016) Critical role for telomerase in the mechanism of flow-mediated dilation in the human microcirculation. Circ Res 118:856–866. https://doi.org/10.1161/circresaha.115.307918 - PubMed
  7. Beyer AM, Zinkevich N, Miller B, Liu Y, Wittenburg AL, Mitchell M, Galdieri R, Sorokin A, Gutterman DD (2017) Transition in the mechanism of flow-mediated dilation with aging and development of coronary artery disease. Basic Res Cardiol 112:5. https://doi.org/10.1007/s00395-016-0594-x - PubMed
  8. Bijkerk R, Duijs JM, Khairoun M, Ter Horst CJ, van der Pol P, Mallat MJ, Rotmans JI, de Vries AP, de Koning EJ, de Fijter JW, Rabelink TJ, van Zonneveld AJ, Reinders ME (2015) Circulating microRNAs associate with diabetic nephropathy and systemic microvascular damage and normalize after simultaneous pancreas-kidney transplantation. Am J Transplant 15:1081–1090. https://doi.org/10.1111/ajt.13072 - PubMed
  9. Calo N, Ramadori P, Sobolewski C, Romero Y, Maeder C, Fournier M, Rantakari P, Zhang FP, Poutanen M, Dufour JF, Humar B, Nef S, Foti M (2016) Stress-activated miR-21/miR-21* in hepatocytes promotes lipid and glucose metabolic disorders associated with high-fat diet consumption. Gut 65:1871–1881. https://doi.org/10.1136/gutjnl-2015-310822 - PubMed
  10. Chen Q, Qiu F, Zhou K, Matlock HG, Takahashi Y, Rajala RVS, Yang Y, Moran E, Ma JX (2017) Pathogenic role of microRNA-21 in diabetic retinopathy through downregulation of PPARα. Diabetes 66:1671–1682. https://doi.org/10.2337/db16-1246 - PubMed
  11. Chin-Dusting JP, Alexander CT, Arnold PJ, Hodgson WC, Lux AS, Jennings GL (1996) Effects of in vivo and in vitro L-arginine supplementation on healthy human vessels. J Cardiovasc Pharmacol 28:158–166. https://doi.org/10.1097/00005344-199607000-00023 - PubMed
  12. Cho SY, Kim SH, Yi MH, Zhang E, Kim E, Park J, Jo EK, Lee YH, Park MS, Kim Y, Park J, Kim DW (2017) Expression of PGC1α in glioblastoma multiforme patients. Oncol Lett 13:4055–4076. https://doi.org/10.3892/ol.2017.5972 - PubMed
  13. Choi M, Lu YW, Zhao J, Wu M, Zhang W, Long X (2020) Transcriptional control of a novel long noncoding RNA Mymsl in smooth muscle cells by a single Cis-element and its initial functional characterization in vessels. J Mol Cell Cardiol 138:147–157. https://doi.org/10.1016/j.yjmcc.2019.11.148 - PubMed
  14. Choi SK, Galan M, Kassan M, Partyka M, Trebak M, Matrougui K (2012) Poly(ADP-ribose) polymerase 1 inhibition improves coronary arteriole function in type 2 diabetes mellitus. Hypertension 59:1060–1068. https://doi.org/10.1161/hypertensionaha.111.190140 - PubMed
  15. Couto GK, Britto LR, Mill JG, Rossoni LV (2015) Enhanced nitric oxide bioavailability in coronary arteries prevents the onset of heart failure in rats with myocardial infarction. J Mol Cell Cardiol 86:110–120. https://doi.org/10.1016/j.yjmcc.2015.07.017 - PubMed
  16. Craige SM, Kroller-Schon S, Li C, Kant S, Cai S, Chen K, Contractor MM, Pei Y, Schulz E, Keaney JF Jr (2016) PGC-1alpha dictates endothelial function through regulation of eNOS expression. Sci Rep 6:38210. https://doi.org/10.1038/srep38210 - PubMed
  17. Dagamajalu S, Rex DAB, Philem PD, Rainey JK, Keshava Prasad TS (2021) A network map of apelin-mediated signaling. J Cell Commun Signal 16(1):137–143 (Netherlands) - PubMed
  18. Dai B, Li H, Fan J, Zhao Y, Yin Z, Nie X, Wang DW, Chen C (2018) MiR-21 protected against diabetic cardiomyopathy induced diastolic dysfunction by targeting gelsolin. Cardiovasc Diabetol 17:123. https://doi.org/10.1186/s12933-018-0767-z - PubMed
  19. Dang X, Du G, Hu W, Ma L, Wang P, Li Y (2019) Peroxisome proliferator-activated receptor gamma coactivator-1α/HSF1 axis effectively alleviates lipopolysaccharide-induced acute lung injury via suppressing oxidative stress and inflammatory response. J Cell Biochem 120:544–551. https://doi.org/10.1002/jcb.27409 - PubMed
  20. Ding M, Feng N, Tang D, Feng J, Li Z, Jia M, Liu Z, Gu X, Wang Y, Fu F, Pei J (2018) Melatonin prevents Drp1-mediated mitochondrial fission in diabetic hearts through SIRT1-PGC1alpha pathway. J Pineal Res 65:e12491. https://doi.org/10.1111/jpi.12491 - PubMed
  21. Dissard R, Klein J, Caubet C, Breuil B, Siwy J, Hoffman J, Sicard L, Ducasse L, Rascalou S, Payre B, Buleon M, Mullen W, Mischak H, Tack I, Bascands JL, Buffin-Meyer B, Schanstra JP (2013) Long term metabolic syndrome induced by a high fat high fructose diet leads to minimal renal injury in C57BL/6 mice. PLoS One 8:e76703. https://doi.org/10.1371/journal.pone.0076703 - PubMed
  22. Duling DR (1994) Simulation of multiple isotropic spin-trap EPR spectra. J Magn Reson B 104:105–110. https://doi.org/10.1006/jmrb.1994.1062 - PubMed
  23. Freed JK, Beyer AM, LoGiudice JA, Hockenberry JC, Gutterman DD (2014) Ceramide changes the mediator of flow-induced vasodilation from nitric oxide to hydrogen peroxide in the human microcirculation. Circ Res 115:525–532. https://doi.org/10.1161/CIRCRESAHA.115.303881 - PubMed
  24. Gomez IG, MacKenna DA, Johnson BG, Kaimal V, Roach AM, Ren S, Nakagawa N, Xin C, Newitt R, Pandya S, Xia TH, Liu X, Borza DB, Grafals M, Shankland SJ, Himmelfarb J, Portilla D, Liu S, Chau BN, Duffield JS (2015) Anti-microRNA-21 oligonucleotides prevent Alport nephropathy progression by stimulating metabolic pathways. J Clin Invest 125:141–156. https://doi.org/10.1172/JCI75852 - PubMed
  25. Hutcheson R, Chaplin J, Hutcheson B, Borthwick F, Proctor S, Gebb S, Jadhav R, Smith E, Russell JC, Rocic P (2014) miR-21 normalizes vascular smooth muscle proliferation and improves coronary collateral growth in metabolic syndrome. Faseb J 28:4088–4099. https://doi.org/10.1096/fj.14-251223 - PubMed
  26. Hutcheson R, Terry R, Hutcheson B, Jadhav R, Chaplin J, Smith E, Barrington R, Proctor SD, Rocic P (2015) miR-21-mediated decreased neutrophil apoptosis is a determinant of impaired coronary collateral growth in metabolic syndrome. Am J Physiol Heart Circ Physiol 308:H1323-1335. https://doi.org/10.1152/ajpheart.00654.2014 - PubMed
  27. Jia G, Hill MA, Sowers JR (2018) Diabetic cardiomyopathy: an update of mechanisms contributing to this clinical entity. Circ Res 122:624–638. https://doi.org/10.1161/CIRCRESAHA.117.311586 - PubMed
  28. Kadlec AO, Barnes C, Durand MJ, Gutterman DD (2018) Microvascular adaptations to exercise: protective effect of PGC-1α. Am J Hypertens 31:240–246. https://doi.org/10.1093/ajh/hpx162 - PubMed
  29. Kadlec AO, Chabowski DS, Ait-Aissa K, Hockenberry JC, Otterson MF, Durand MJ, Freed JK, Beyer AM, Gutterman DD (2017) PGC-1α (Peroxisome Proliferator-Activated Receptor gamma Coactivator 1-α) overexpression in coronary artery disease recruits NO and hydrogen peroxide during flow-mediated dilation and protects against increased intraluminal pressure. Hypertension 70:166–173. https://doi.org/10.1161/HYPERTENSIONAHA.117.09289 - PubMed
  30. Kang PT, Chen CL, Ohanyan V, Luther DJ, Meszaros JG, Chilian WM, Chen YR (2015) Overexpressing superoxide dismutase 2 induces a supernormal cardiac function by enhancing redox-dependent mitochondrial function and metabolic dilation. J Mol Cell Cardiol 88:14–28. https://doi.org/10.1016/j.yjmcc.2015.09.001 - PubMed
  31. Kaur R, Kaur M, Singh J (2018) Endothelial dysfunction and platelet hyperactivity in type 2 diabetes mellitus: molecular insights and therapeutic strategies. Cardiovasc Diabetol 17:121. https://doi.org/10.1186/s12933-018-0763-3 - PubMed
  32. Keleher MR, Erickson K, Smith HA, Kechris KJ, Yang IV, Dabelea D, Friedman JE, Boyle KE, Jansson T (2021) Placental insulin/IGF-1 signaling, PGC-1α, and inflammatory pathways are associated with metabolic outcomes at 4–6 years of age: the ECHO healthy start cohort. Diabetes 70:745–751. https://doi.org/10.2337/db20-0902 - PubMed
  33. Labazi H, Trask AJ (2017) Coronary microvascular disease as an early culprit in the pathophysiology of diabetes and metabolic syndrome. Pharmacol Res 123:114–121. https://doi.org/10.1016/j.phrs.2017.07.004 - PubMed
  34. Langbein H, Brunssen C, Hofmann A, Cimalla P, Brux M, Bornstein SR, Deussen A, Koch E, Morawietz H (2016) NADPH oxidase 4 protects against development of endothelial dysfunction and atherosclerosis in LDL receptor deficient mice. Eur Heart J 37:1753–1761. https://doi.org/10.1093/eurheartj/ehv564 - PubMed
  35. Lau P, Nixon SJ, Parton RG, Muscat GE (2004) RORα regulates the expression of genes involved in lipid homeostasis in skeletal muscle cells: caveolin-3 and CPT-1 are direct targets of ROR. J Biol Chem 279:36828–36840. https://doi.org/10.1074/jbc.M404927200 - PubMed
  36. Li X, Wei Y, Wang Z (2018) microRNA-21 and hypertension. Hypertens Res 41:649–661. https://doi.org/10.1038/s41440-018-0071-z - PubMed
  37. Liu H, Lessieur EM, Saadane A, Lindstrom SI, Taylor PR, Kern TS (2019) Neutrophil elastase contributes to the pathological vascular permeability characteristic of diabetic retinopathy. Diabetologia 62(12):2365–2374 - PubMed
  38. Liu Y, Zhao H, Li H, Kalyanaraman B, Nicolosi AC, Gutterman DD (2003) Mitochondrial sources of H - PubMed
  39. Luo S, Truong AH, Makino A (2016) Isolation of mouse coronary endothelial cells. J Vis Exp. https://doi.org/10.3791/53985 - PubMed
  40. Luther KM, Haar L, McGuinness M, Wang Y, Lynch Iv TL, Phan A, Song Y, Shen Z, Gardner G, Kuffel G, Ren X, Zilliox MJ, Jones WK (2018) Exosomal miR-21a-5p mediates cardioprotection by mesenchymal stem cells. J Mol Cell Cardiol 119:125–137. https://doi.org/10.1016/j.yjmcc.2018.04.012 - PubMed
  41. Majithiya JB, Paramar AN, Balaraman R (2005) Pioglitazone, a PPARγ agonist, restores endothelial function in aorta of streptozotocin-induced diabetic rats. Cardiovasc Res 66:150–161. https://doi.org/10.1016/j.cardiores.2004.12.025 - PubMed
  42. Matoba T, Shimokawa H, Nakashima M, Hirakawa Y, Mukai Y, Hirano K, Kanaide H, Takeshita A (2000) Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in mice. J Clin Invest 106:1521–1530. https://doi.org/10.1172/jci10506 - PubMed
  43. Miura H, Bosnjak JJ, Ning G, Saito T, Miura M, Gutterman DD (2003) Role for hydrogen peroxide in flow-induced dilation of human coronary arterioles. Circ Res 92:e31-40. https://doi.org/10.1161/01.res.0000054200.44505.ab - PubMed
  44. Miura H, Wachtel RE, Liu Y, Loberiza FR Jr, Saito T, Miura M, Gutterman DD (2001) Flow-induced dilation of human coronary arterioles: important role of Ca(2+)-activated K(+) channels. Circulation 103:1992–1998. https://doi.org/10.1161/01.cir.103.15.1992 - PubMed
  45. Murthy VL, Naya M, Foster CR, Gaber M, Hainer J, Klein J, Dorbala S, Blankstein R, Di Carli MF (2012) Association between coronary vascular dysfunction and cardiac mortality in patients with and without diabetes mellitus. Circulation 126:1858–1868. https://doi.org/10.1161/CIRCULATIONAHA.112.120402 - PubMed
  46. Nishiyama SK, Zhao J, Wray DW, Richardson RS (2017) Vascular function and endothelin-1: tipping the balance between vasodilation and vasoconstriction. J Appl Physiol (1985) 122:354–360. https://doi.org/10.1152/japplphysiol.00772.2016 - PubMed
  47. Ohanyan V, Yin L, Bardakjian R, Kolz C, Enrick M, Hakobyan T, Kmetz J, Bratz I, Luli J, Nagane M, Khan N, Hou H, Kuppusamy P, Graham J, Fu FK, Janota D, Oyewumi MO, Logan S, Lindner JR, Chilian WM (2015) Requisite role of Kv1.5 channels in coronary metabolic dilation. Circ Res 117:612–621. https://doi.org/10.1161/CIRCRESAHA.115.306642 - PubMed
  48. Ohanyan V, Yin L, Bardakjian R, Kolz C, Enrick M, Hakobyan T, Luli J, Graham K, Khayata M, Logan S, Kmetz J, Chilian WM (2017) Kv1.3 channels facilitate the connection between metabolism and blood flow in the heart. Microcirculation. https://doi.org/10.1111/micc.12334 - PubMed
  49. Oishi K, Yamamoto S, Itoh N, Nakao R, Yasumoto Y, Tanaka K, Kikuchi Y, Fukudome S, Okita K, Takano-Ishikawa Y (2015) Wheat alkylresorcinols suppress high-fat, high-sucrose diet-induced obesity and glucose intolerance by increasing insulin sensitivity and cholesterol excretion in male mice. J Nutr 145:199–206. https://doi.org/10.3945/jn.114.202754 - PubMed
  50. Ormazabal V, Nair S, Elfeky O, Aguayo C, Salomon C, Zuniga FA (2018) Association between insulin resistance and the development of cardiovascular disease. Cardiovasc Diabetol 17:122. https://doi.org/10.1186/s12933-018-0762-4 - PubMed
  51. Park Y, Yang J, Zhang H, Chen X, Zhang C (2011) Effect of PAR2 in regulating TNF-α and NAD(P)H oxidase in coronary arterioles in type 2 diabetic mice. Basic Res Cardiol 106:111–123. https://doi.org/10.1007/s00395-010-0129-9 - PubMed
  52. Qiao L, Hu S, Liu S, Zhang H, Ma H, Huang K, Li Z, Su T, Vandergriff A, Tang J, Allen T, Dinh PU, Cores J, Yin Q, Li Y, Cheng K (2019) microRNA-21-5p dysregulation in exosomes derived from heart failure patients impairs regenerative potential. J Clin Invest 129:2237–2250. https://doi.org/10.1172/JCI123135 - PubMed
  53. Ramanujam D, Schon AP, Beck C, Vaccarello P, Felician G, Dueck A, Esfandyari D, Meister G, Meitinger T, Schulz C, Engelhardt S (2021) MicroRNA-21-dependent macrophage-to-fibroblast signaling determines the cardiac response to pressure overload. Circulation 143:1513–1525. https://doi.org/10.1161/CIRCULATIONAHA.120.050682 - PubMed
  54. Ranjan P, Kumari R, Goswami SK, Li J, Pal H, Suleiman Z, Cheng Z, Krishnamurthy P, Kishore R, Verma SK (2021) Myofibroblast-derived exosome induce cardiac endothelial cell dysfunction. Front Cardiovasc Med 8:676267. https://doi.org/10.3389/fcvm.2021.676267 - PubMed
  55. Rughani A, Friedman JE, Tryggestad JB (2020) Type 2 diabetes in youth: the role of early life exposures. Curr Diab Rep 20:45. https://doi.org/10.1007/s11892-020-01328-6 - PubMed
  56. Sato A, Sakuma I, Gutterman DD (2003) Mechanism of dilation to reactive oxygen species in human coronary arterioles. Am J Physiol Heart Circ Physiol 285:H2345-2354. https://doi.org/10.1152/ajpheart.00458.2003 - PubMed
  57. Seeger FH, Sedding D, Langheinrich AC, Haendeler J, Zeiher AM, Dimmeler S (2009) Inhibition of the p38 MAP kinase in vivo improves number and functional activity of vasculogenic cells and reduces atherosclerotic disease progression. Basic Res Cardiol 105:389–397. https://doi.org/10.1007/s00395-009-0072-9 - PubMed
  58. Sekar D, Venugopal B, Sekar P, Ramalingam K (2016) Role of microRNA 21 in diabetes and associated/related diseases. Gene 582:14–18. https://doi.org/10.1016/j.gene.2016.01.039 - PubMed
  59. Sharabi K, Lin H, Tavares CDJ, Dominy JE, Camporez JP, Perry RJ, Schilling R, Rines AK, Lee J, Hickey M, Bennion M, Palmer M, Nag PP, Bittker JA, Perez J, Jedrychowski MP, Ozcan U, Gygi SP, Kamenecka TM, Shulman GI, Schreiber SL, Griffin PR, Puigserver P (2017) Selective chemical inhibition of PGC-1α gluconeogenic activity ameliorates type 2 diabetes. Cell 169:148–160. https://doi.org/10.1016/j.cell.2017.03.001 (e115) - PubMed
  60. Shimokawa H (2010) Hydrogen peroxide as an endothelium-derived hyperpolarizing factor. Pflugers Arch 459:915–922. https://doi.org/10.1007/s00424-010-0790-8 - PubMed
  61. Simonsen U, Prieto D, Mulvany MJ, Ehrnrooth E, Korsgaard N, Nyborg NC (1992) Effect of induced hypercholesterolemia in rabbits on functional responses of isolated large proximal and small distal coronary arteries. Arterioscler Thromb 12:380–392. https://doi.org/10.1161/01.atv.12.3.380 - PubMed
  62. St-Pierre J, Drori S, Uldry M, Silvaggi JM, Rhee J, Jager S, Handschin C, Zheng K, Lin J, Yang W, Simon DK, Bachoo R, Spiegelman BM (2006) Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 127:397–408. https://doi.org/10.1016/j.cell.2006.09.024 - PubMed
  63. Surwit RS, Kuhn CM, Cochrane C, McCubbin JA, Feinglos MN (1988) Diet-induced type II diabetes in C57BL/6J mice. Diabetes 37:1163–1167. https://doi.org/10.2337/diab.37.9.1163 - PubMed
  64. Takaki A, Morikawa K, Tsutsui M, Murayama Y, Tekes E, Yamagishi H, Ohashi J, Yada T, Yanagihara N, Shimokawa H (2008) Crucial role of nitric oxide synthases system in endothelium-dependent hyperpolarization in mice. J Exp Med 205:2053–2063. https://doi.org/10.1084/jem.20080106 - PubMed
  65. Tavares CDJ, Aigner S, Sharabi K, Sathe S, Mutlu B, Yeo GW, Puigserver P (2020) Transcriptome-wide analysis of PGC-1α-binding RNAs identifies genes linked to glucagon metabolic action. Proc Natl Acad Sci USA 117:22204–22213. https://doi.org/10.1073/pnas.2000643117 - PubMed
  66. Urbich C, Kuehbacher A, Dimmeler S (2008) Role of microRNAs in vascular diseases, inflammation, and angiogenesis. Cardiovasc Res 79:581–588. https://doi.org/10.1093/cvr/cvn156 - PubMed
  67. van de Wouw J, Sorop O, van Drie RWA, van Duin RWB, Nguyen ITN, Joles JA, Verhaar MC, Merkus D, Duncker DJ (2020) Perturbations in myocardial perfusion and oxygen balance in swine with multiple risk factors: a novel model of ischemia and no obstructive coronary artery disease. Basic Res Cardiol 115:21. https://doi.org/10.1007/s00395-020-0778-2 - PubMed
  68. Wang D, Deuse T, Stubbendorff M, Chernogubova E, Erben RG, Eken SM, Jin H, Li Y, Busch A, Heeger CH, Behnisch B, Reichenspurner H, Robbins RC, Spin JM, Tsao PS, Schrepfer S, Maegdefessel L (2015) Local microRNA modulation using a novel anti-miR-21-eluting stent effectively prevents experimental in-stent restenosis. Arterioscler Thromb Vasc Biol 35:1945–1953. https://doi.org/10.1161/ATVBAHA.115.305597 - PubMed
  69. Wang Z, Wu Y, Zhang S, Zhao Y, Yin X, Wang W, Ma X, Liu H (2019) The role of NO-cGMP pathway inhibition in vascular endothelial-dependent smooth muscle relaxation disorder of AT1-AA positive rats: protective effects of adiponectin. Nitric Oxide 87:10–22. https://doi.org/10.1016/j.niox.2019.02.006 - PubMed
  70. Weber M, Baker MB, Moore JP, Searles CD (2010) MiR-21 is induced in endothelial cells by shear stress and modulates apoptosis and eNOS activity. Biochem Biophys Res Commun 393:643–648. https://doi.org/10.1016/j.bbrc.2010.02.045 - PubMed
  71. Weil BR, Canty JM Jr (2014) Ceramide signaling in the coronary microcirculation: a double-edged sword? Circ Res 115:475–477. https://doi.org/10.1161/circresaha.114.304589 - PubMed
  72. Weitzberg E, Hezel M, Lundberg JO (2010) Nitrate-nitrite-nitric oxide pathway: implications for anesthesiology and intensive care. Anesthesiology 113:1460–1475. https://doi.org/10.1097/ALN.0b013e3181fcf3cc - PubMed
  73. Xu X, Jiao X, Song N, Luo W, Liang M, Ding X, Teng J (2017) Role of miR21 on vascular endothelial cells in the protective effect of renal delayed ischemic preconditioning. Mol Med Rep 16:2627–2635. https://doi.org/10.3892/mmr.2017.6870 - PubMed
  74. Xu Y, Zalzala M, Xu J, Li Y, Yin L, Zhang Y (2015) A metabolic stress-inducible miR-34a-HNF4alpha pathway regulates lipid and lipoprotein metabolism. Nat Commun 6:7466. https://doi.org/10.1038/ncomms8466 - PubMed
  75. Zhang Z, Peng H, Chen J, Chen X, Han F, Xu X, He X, Yan N (2009) MicroRNA-21 protects from mesangial cell proliferation induced by diabetic nephropathy in db/db mice. FEBS Lett 583:2009–2014. https://doi.org/10.1016/j.febslet.2009.05.021 - PubMed

Publication Types

Grant support