open access

Vol 83, No 1 (2024): Folia Morphologica
Original article
Submitted: 2023-02-10
Accepted: 2023-03-21
Published online: 2023-04-20
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TLN1 synergizes with ITGA5 to ameliorate cardiac microvascular endothelial cell dysfunction

Xianfeng Wang1, Wenkai Mao2, Xiaofeng Ma3
·
Pubmed: 37144848
·
Folia Morphol 2024;83(1):92-101.
Affiliations
  1. Emergency Department, Qinghai Cardio-Cerebrovascular Specialty Hospital, Qinghai High Altitude Medical Research Institute, Xining, Qinghai, P.R. China
  2. Medical Department, Qinghai Cardio-Cerebrovascular Specialty Hospital, Qinghai High Altitude Medical Research Institute, Xining, Qinghai, P.R. China
  3. Personnel Department, Qinghai Cardio-Cerebrovascular Specialty Hospital, Qinghai High Altitude Medical Research Institute, Xining, Qinghai, P.R. China

open access

Vol 83, No 1 (2024): Folia Morphologica
ORIGINAL ARTICLES
Submitted: 2023-02-10
Accepted: 2023-03-21
Published online: 2023-04-20

Abstract

Background: The complex process of atherosclerosis is thought to begin with endothelial cell dysfunction, and advanced atherosclerosis is the underlying cause of coronary artery disease (CAD). Uncovering the underlying mechanisms of CAD-related endothelial cell injury may contribute to the treatment.

Materials and methods: Cardiac microvascular endothelial cells (CMVECs) were treated with oxidised low-density lipoprotein (ox-LDL) to mimic an injury model. The involvement of Talin-1 (TLN1) and integrin alpha 5 (ITGA5) in the proliferation, apoptosis, angiogenesis, inflammatory response, and oxidative stress in CMVECs were assessed.

Results: TLN1 overexpression assisted CMVECs in resistance to ox-LDL stimulation, with alleviated cell proliferation and angiogenesis, reduced apoptosis, inflammatory response, and oxidative stress. TLN1 overexpression triggered increased ITGA5, and ITGA5 knockdown reversed the effects of TLN1 overexpression on the abovementioned aspects. Together, TLN1 synergized with ITGA5 to ameliorate the dysfunction in CMVECs.

Conclusions: This finding suggests their probable involvement in CAD, and increasing their levels is beneficial to disease relief.

Abstract

Background: The complex process of atherosclerosis is thought to begin with endothelial cell dysfunction, and advanced atherosclerosis is the underlying cause of coronary artery disease (CAD). Uncovering the underlying mechanisms of CAD-related endothelial cell injury may contribute to the treatment.

Materials and methods: Cardiac microvascular endothelial cells (CMVECs) were treated with oxidised low-density lipoprotein (ox-LDL) to mimic an injury model. The involvement of Talin-1 (TLN1) and integrin alpha 5 (ITGA5) in the proliferation, apoptosis, angiogenesis, inflammatory response, and oxidative stress in CMVECs were assessed.

Results: TLN1 overexpression assisted CMVECs in resistance to ox-LDL stimulation, with alleviated cell proliferation and angiogenesis, reduced apoptosis, inflammatory response, and oxidative stress. TLN1 overexpression triggered increased ITGA5, and ITGA5 knockdown reversed the effects of TLN1 overexpression on the abovementioned aspects. Together, TLN1 synergized with ITGA5 to ameliorate the dysfunction in CMVECs.

Conclusions: This finding suggests their probable involvement in CAD, and increasing their levels is beneficial to disease relief.

Get Citation

Keywords

Talin-1, integrin, coronary artery disease, cardiac microvascular endothelial cells, atherosclerosis

About this article
Title

TLN1 synergizes with ITGA5 to ameliorate cardiac microvascular endothelial cell dysfunction

Journal

Folia Morphologica

Issue

Vol 83, No 1 (2024): Folia Morphologica

Article type

Original article

Pages

92-101

Published online

2023-04-20

Page views

696

Article views/downloads

488

DOI

10.5603/FM.a2023.0031

Pubmed

37144848

Bibliographic record

Folia Morphol 2024;83(1):92-101.

Keywords

Talin-1
integrin
coronary artery disease
cardiac microvascular endothelial cells
atherosclerosis

Authors

Xianfeng Wang
Wenkai Mao
Xiaofeng Ma

References (37)
  1. Aherrahrou R, Guo L, Nagraj VP, et al. Genetic regulation of atherosclerosis-relevant phenotypes in human vascular smooth muscle cells. Circ Res. 2020; 127(12): 1552–1565.
  2. Bidault G, Garcia M, Capeau J, et al. Progerin expression induces inflammation, oxidative stress and senescence in human coronary endothelial cells. Cells. 2020; 9(5).
  3. Chakraborty S, Banerjee S, Raina M, et al. Force-Directed "mechanointeractome" of talin-integrin. Biochemistry. 2019; 58(47): 4677–4695.
  4. Chen G, Xu C, Gillette TG, et al. Cardiomyocyte-derived small extracellular vesicles can signal eNOS activation in cardiac microvascular endothelial cells to protect against Ischemia/Reperfusion injury. Theranostics. 2020; 10(25): 11754–11774.
  5. Demos C, Williams D, Jo H. Disturbed flow induces atherosclerosis by annexin A2-mediated integrin activation. Circ Res. 2020; 127(8): 1091–1093.
  6. Fan L, Zhou W, Zhang L, et al. Sitagliptin protects against hypoxia/reoxygenation (H/R)-induced cardiac microvascular endothelial cell injury. Am J Transl Res. 2019; 11(4): 2099–2107.
  7. Finney AC, Stokes KY, Pattillo CB, et al. Integrin signaling in atherosclerosis. Cell Mol Life Sci. 2017; 74(12): 2263–2282.
  8. Fukaya H, Ako J, Yasuda S, et al. Aspirin versus P2Y inhibitors with anticoagulation therapy for atrial fibrillation. Heart. 2021; 107(21): 1731–1738.
  9. Gholipour A, Shakerian F, Zahedmehr A, et al. Downregulation of Talin-1 is associated with the increased expression of miR-182-5p and miR-9-5p in coronary artery disease. J Clin Lab Anal. 2022; 36(4): e24252.
  10. Guo X, Jiang H, Chen J, et al. RP105 ameliorates hypoxia̸reoxygenation injury in cardiac microvascular endothelial cells by suppressing TLR4̸MAPKs̸NF-κB signaling. Int J Mol Med. 2018; 42(1): 505–513.
  11. Hu J, Zheng Z, Li X, et al. Metformin attenuates hypoxia-induced endothelial cell injury by activating the amp-activated protein kinase pathway. J Cardiovasc Pharmacol. 2021; 77(6): 862–874.
  12. Jin H, Zhu Yi, Li Y, et al. BDNF-mediated mitophagy alleviates high-glucose-induced brain microvascular endothelial cell injury. Apoptosis. 2019; 24(5-6): 511–528.
  13. Khera AV, Kathiresan S. Genetics of coronary artery disease: discovery, biology and clinical translation. Nat Rev Genet. 2017; 18(6): 331–344.
  14. Liu M, Solomon W, Cespedes JC, et al. Neuregulin-1 attenuates experimental cerebral malaria (ECM) pathogenesis by regulating ErbB4/AKT/STAT3 signaling. J Neuroinflammation. 2018; 15(1): 104.
  15. Malakar AKr, Choudhury D, Halder B, et al. A review on coronary artery disease, its risk factors, and therapeutics. J Cell Physiol. 2019; 234(10): 16812–16823.
  16. Marx C, Novotny J, Salbeck D, et al. Eosinophil-platelet interactions promote atherosclerosis and stabilize thrombosis with eosinophil extracellular traps. Blood. 2019; 134(21): 1859–1872.
  17. Schumacher JA, Wright ZA, Owen ML, et al. Integrin α5 and Integrin α4 cooperate to promote endocardial differentiation and heart morphogenesis. Dev Biol. 2020; 465(1): 46–57.
  18. Sun Z, Costell M, Fässler R. Integrin activation by talin, kindlin and mechanical forces. Nat Cell Biol. 2019; 21(1): 25–31.
  19. Szklarczyk D, Gable AL, Nastou KC, et al. The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res. 2021; 49(D1): D605–D612.
  20. Timofeeva M, Ooi A, Poon EKW, et al. Numerical simulation of the blood flow through the coronary artery stenosis: Effects of varying eccentricity. Comput Biol Med. 2022; 146: 105672.
  21. Tuso P, Stoll SR, Li WW. A plant-based diet, atherogenesis, and coronary artery disease prevention. Perm J. 2015; 19(1): 62–67.
  22. Vermeulen Z, Mateiu L, Dugaucquier L, et al. Cardiac endothelial cell transcriptome in neonatal, adult, and remodeling hearts. Physiol Genomics. 2019; 51(6): 186–196.
  23. Wang J, Zhang H, Du A, et al. DJ-1 alleviates anoxia and hypoglycemia injury in cardiac microvascular via AKT and GSH. Mol Cell Probes. 2020; 53: 101600.
  24. Wang YY, Duan H, Wang S, et al. Upregulated Talin1 synergistically boosts β-estradiol-induced proliferation and pro-angiogenesis of eutopic and ectopic endometrial stromal cells in adenomyosis. Reprod Biol Endocrinol. 2021; 19(1): 70.
  25. Wang Y, Zhang Yu, Li J, et al. Role of Mydgf in the regulation of hypoxia/reoxygenation-induced apoptosis in cardiac microvascular endothelial cells. In Vitro Cell Dev Biol Anim. 2022; 58(8): 669–678.
  26. Wei X, Sun Y, Wu Y, et al. Downregulation of Talin-1 expression associates with increased proliferation and migration of vascular smooth muscle cells in aortic dissection. BMC Cardiovasc Disord. 2017; 17(1): 162.
  27. Xu F, Zhou F. Inhibition of microRNA-92a ameliorates lipopolysaccharide-induced endothelial barrier dysfunction by targeting ITGA5 through the PI3K/Akt signaling pathway in human pulmonary microvascular endothelial cells. Int Immunopharmacol. 2020; 78: 106060.
  28. Xu RX, Wu YJ. Lipid-Modifying drugs: pharmacology and perspectives. Adv Exp Med Biol. 2020; 1177: 133–148.
  29. Ye Q, Ju C, Ye Z, et al. Circ_ROBO2/miR-186-5p/TRIM14 axis regulates oxidized low-density lipoprotein-induced cardiac microvascular endothelial cell injury. Regen Ther. 2022; 20: 138–146.
  30. Yun S, Hu R, Schwaemmle ME, et al. Integrin α5β1 regulates PP2A complex assembly through PDE4D in atherosclerosis. J Clin Invest. 2019; 129(11): 4863–4874.
  31. Zhang Q, Cao Y, Liu Y, et al. Shear stress inhibits cardiac microvascular endothelial cells apoptosis to protect against myocardial ischemia reperfusion injury via YAP/miR-206/PDCD4 signaling pathway. Biochem Pharmacol. 2021; 186: 114466.
  32. Zhang Z, Tang J, Song J, et al. Elabela alleviates ferroptosis, myocardial remodeling, fibrosis and heart dysfunction in hypertensive mice by modulating the IL-6/STAT3/GPX4 signaling. Free Radic Biol Med. 2022; 181: 130–142.
  33. Zhao BS, Belhoul-Fakir H, Jansen S, et al. Major gaps in human evidence for structure and function of the vasa vasora limit our understanding of the link with atherosclerosis. J Anat. 2021; 238(3): 785–793.
  34. Zhong CM, Li S, Wang XW, et al. MicroRNA-92a -mediated endothelial to mesenchymal transition controls vein graft neointimal lesion formation. Exp Cell Res. 2021; 398(1): 112402.
  35. Zhou H, Wang S, Zhu P, et al. Empagliflozin rescues diabetic myocardial microvascular injury via AMPK-mediated inhibition of mitochondrial fission. Redox Biol. 2018; 15: 335–346.
  36. Zhou H, Zhang Y, Hu S, et al. Melatonin protects cardiac microvasculature against ischemia/reperfusion injury via suppression of mitochondrial fission-VDAC1-HK2-mPTP-mitophagy axis. J Pineal Res. 2017; 63(1).
  37. Zou R, Shi W, Qiu J, et al. Empagliflozin attenuates cardiac microvascular ischemia/reperfusion injury through improving mitochondrial homeostasis. Cardiovasc Diabetol. 2022; 21(1): 106.

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