SavedAdd your journal

Journals / Turkish Journal of Medical Sciences / 2018 / Cilt: 48 - Sayı: 6

Losartan inhibits EGFR transactivation in vascular smooth muscle cells

Akın YEŞİLKAYA
Mustafa KIRÇA
Pages
1364–1371
Publication Date
2022-11-03
DOI
—
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

EGFR inhibition is a candidate therapy for combating cardiovasculardiseases such as hypertension and atherosclerosis.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Background/aim: Angiotensin II (Ang II)-induced molecular signaling pathways play a significant role in the progression ofcardiovascular diseases, including hypertension and atherosclerosis.
📊
Key Findings & Data:Ang II-inducedEGFR phosphorylation (tyrosine 1068) and ERK1/2 MAPK phosphorylation (threonine 202 and tyrosine 204) were evaluated bywestern blotting.Results: Ang II induced EGFR phosphorylation through the Ang II type I receptor (P < 0.05).
💡
Conclusion & Impact:EGFR inhibition is a candidate therapy for combating cardiovasculardiseases such as hypertension and atherosclerosis.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Domain Parameters

Abstract

Background/aim: Angiotensin II (Ang II)-induced molecular signaling pathways play a significant role in the progression ofcardiovascular diseases, including hypertension and atherosclerosis. In addition to the well-known effects of Ang II, it may activateepidermal growth factor receptor (EGFR) in a process known as transactivation, which contributes to vascular pathologies. The aimof this study was to determine whether losartan could reduce EGFR transactivation induced by Ang II. Additionally, we evaluated theroles of heparin-binding epidermal-like growth factor (HB-EGF) and matrix metalloproteinases (MMPs) in Ang II-induced EGFRtransactivation.Materials and methods: Vascular smooth muscle cells were isolated from a rat aorta and grown in primary culture. Ang II-inducedEGFR phosphorylation (tyrosine 1068) and ERK1/2 MAPK phosphorylation (threonine 202 and tyrosine 204) were evaluated bywestern blotting.Results: Ang II induced EGFR phosphorylation through the Ang II type I receptor (P < 0.05). The transactivation process was inhibitedby losartan and mediated by HB-EGF and MMPs. Ang II transactivates EGFR in an AT1R-dependent manner.Conclusion: The results of this study show that losartan, a widely used antihypertensive agent, can suppress EGFR phosphorylation(Y1068) upon Ang II stimulation in vascular smooth muscle cells. EGFR inhibition is a candidate therapy for combating cardiovasculardiseases such as hypertension and atherosclerosis.

🔖

Cite This Article

YEŞİLKAYA, A., KIRÇA, M. (2022). Losartan inhibits EGFR transactivation in vascular smooth muscle cells. Turkish Journal of Medical Sciences, Cilt: 48 - Sayı: 6, 1364–1371. https://ajindex.com/articles/610138

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (10)

  1. Herrington W, Lacey B, Sherliker P, Armitage J, Lewington S. Epidemiology of atherosclerosis and the potential to reduce the global burden of atherothrombotic disease. Circ Res 2016; 118: 535-546.
  2. Bennett MR, Sinha S, Owens GK. Vascular smooth muscle cells in atherosclerosis. Circ Res 2016; 118: 692-702.
  3. Vukelic S, Griendling KK. Angiotensin II, from vasoconstrictor to growth factor: a paradigm shift. Circ Res 2014; 114: 754-757.
  4. Das S, Senapati P, Chen Z, Reddy MA, Ganguly R, Lanting L, Mandi V, Bansal A, Leung A, Zhang S et al. Regulation of angiotensin II actions by enhancers and super-enhancers in vascular smooth muscle cells. Nat Commun 2017; 8: 1467. Kumar R, Singh VP, Baker KM. The intracellular reninangiotensin system: a new paradigm. Trends Endocrin Met 2007; 18: 208-214.
  5. Montezano AC, Nguyen Dinh Cat A, Rios FJ, Touyz RM. Angiotensin II and vascular injury. Curr Hypertens Rep 2014; 16: 431. Chen J, Chen JK, Neilson EG, Harris RC. Role of EGF receptor activation in angiotensin II-induced renal epithelial cell hypertrophy. J Am Soc Nephrol 2006; 17: 1615-1623.
  6. Ohtsu H, Dempsey PJ, Frank GD, Brailoiu E, Higuchi S, Suzuki H, Nakashima H, Eguchi K, Eguchi S. ADAM17 mediates epidermal growth factor receptor transactivation and vascular smooth muscle cell hypertrophy induced by angiotensin II. Arterioscl Thromb Vas 2006; 26: e133-137. Yang X, Zhu MJ, Sreejayan N, Ren J, Du M. Angiotensin II promotes smooth muscle cell proliferation and migration through release of heparin-binding epidermal growth factor and activation of EGF-receptor pathway. Mol Cells 2005; 20: 263-270.
  7. Ge L, Zhang G, You B, Cheng G, Chen L, Shi R. The role of losartan in preventing vascular remodeling in spontaneously hypertensive rats by inhibition of the H2O2/VPO1/HOCl/ MMPs pathway. Biochem Bioph Res Co 2017; 493: 855-861.
  8. Makki N, Thiel KW, Miller FJ. The epidermal growth factor receptor and its ligands in cardiovascular disease. Int J Mol Sci 2013; 14: 20597-20613.
  9. Dreux AC, Lamb DJ, Modjtahedi H, Ferns GA. The epidermal growth factor receptors and their family of ligands: their putative role in atherogenesis. Atherosclerosis 2006; 186: 38- 53. Takahashi M, Hayashi K, Yoshida K, Ohkawa Y, Komurasaki T, Kitabatake A, Ogawa A, Nishida W, Yano M, Monden M et al. Epiregulin as a major autocrine/paracrine factor released from ERK- and p38 MAPK-activated vascular smooth muscle cells. Circulation 2003; 108: 2524-2529.
  10. Mazak I, Fiebeler A, Muller DN, Park JK, Shagdarsuren E, Lindschau C,