mersin univ saglık bilim derg

Mersin Üniversitesi Sağlık Bilimleri Dergisi

1308-0830

Mersin University

10.26559/mersinsbd.531295

Health Care Administration

Sağlık Kurumları Yönetimi

Raynaud Fenomeni üzerine genetik yapı, östrojen ve toksik ajanların klinik etkileri

The clinical effects of genetic structure, estrogen, and toxic agents on Raynaud’s Phenomenon

https://orcid.org/0000-0002-5884-2986

Akkapulu

Merih

MERSİN ÜNİVERSİTESİ, ECZACILIK FAKÜLTESİ, TEMEL ECZACILIK BİLİMLERİ BÖLÜMÜ, BİYOKİMYA ANABİLİM DALI

https://orcid.org/0000-0002-3351-6885

Yalın

Ali Erdinç

MERSİN ÜNİVERSİTESİ, ECZACILIK FAKÜLTESİ, TEMEL ECZACILIK BİLİMLERİ BÖLÜMÜ, BİYOKİMYA ANABİLİM DALI

04 28 2019

12 1 143 149 02 22 2019 03 16 2019

2008

Mersin Üniversitesi Sağlık Bilimleri Dergisi

Raynaud Fenomeni (RF) soğuk kaynaklı vazokonstrüksiyonlakarakterize bir hastalıktır. Bu güçlendirilmiş vazokonstrüksiyon, sempatiksinir sistemi yoluyla soğumaya karşı bir refleks cevabı ve Alfa2C (α2C)adrenoreseptörlerinin lokal aktivasyonu ile gerçekleşmektedir. Bu hastalıkklinik olarak primer ve sekonder olarak sınıflandırılmaktadır. Primer RFidiyopatiktir ve hastalığın en yaygın şeklidir. Sekonder RF, otoimmün veyakanser gibi hastalıklara eşlik edebileceği gibi, sigara içimi ya da bazıilaçların kullanımı da sebebiyet verebilmektedir. Etkilenen bireyler, soğuk vestresin tetiklemesiyle birlikte, genellikle el parmaklarında, klasik üç renkdeğişikliğiyle (solukluk, siyanoz ve hiperemi) ilişkili olan vazospastikataklardan muzdarip olmaktadırlar. Epidemiyolojik çalışmalardan elde edilenveriler, RF prevalansı ile ilgili ilginç bulgular ortaya koymuştur. Yaşlarıaynı olan kadınların, erkeklere göre anlamlı olarak daha yüksek bir insidansasahip olduğu belirlenmiştir. Bu derlemede, östrojenin, genetik yapının vekimyasal ajanların RF üzerine olan etkileri tartışılmıştır. Sonuç olarak, buhastalığa neden olan birçok faktör açıklanmasına rağmen, RF'nin başlangıcınınve ilerlemesinin altında yatan moleküler mekanizmaların aydınlatılması içindaha fazla araştırmaya gereksinim duyulmaktadır.

Raynaud’sphenomenon (RP) is characterized by cold-induced vasoconstriction. Thisenhanced vasoconstriction is achieved by a reflex response to cooling throughthe sympathetic nervous system and by local activation of Alpha2C (α2C)adrenoreceptors. This disease is clinicallyclassified as primary and secondary. Primary RP is idiopathic and is the mostcommon form of the disease. Secondary RP may be associated with diseases suchas autoimmune diseases or cancer, and smoking or the use of certain medicationsmay also be cause. Affected individuals suffer from vasospastic attacksassociated with classical three colour changes (paleness, cyanosis, and hyperemia), often triggered by coldand/or stress. The data from the epidemiological studies revealed interestingfindings related to the prevalence of RP.It was determined that women with the same age had asignificantly higher incidence than men. In this review, the effects ofoestrogen, genetic structure and chemical agents on RP were discussed. As aresult, although many factors have been described causing this disease, furtherresearch is needed to elucidate the molecular mechanisms underlying the onsetand progression of RP.

Raynaud fenomeni vazospazm Alfa2(α2) adrenoreseptörler östrojen

Raynaud's phenomenon vasospasm Alpha2 (α2) adrenoreceptors estrogen

1.Charkoudian N. Mechanisms and modifiers of reflex induced cutaneous vasodilation and vasoconstriction in humans. J. Appl. Physiol. 2010; 109(1985):1221–1228.

2.Wigley FM, Flavahan NA.Raynaud’s phenomenon.N.Engl.J.Med. 2016;375:556–565.

3.Herrick AL. The pathogenesis, diagnosis and treatment of Raynaud phenomenon. Nat. Rev. Rheumatol. 2012;8:469–479.

4.Block JA, Sequeira W. Raynaud’s phenomenon. Lancet 2001;357:2042–2048.

5. Roustit M, Khouri C, Blaise S, Villier C, Carpentier P, Cracowski JL. Pharmacology of Raynaud’s phenomenon. Therapie 2014;69:115–128.

6. Prete M, Fatone MC, Favoino E, Perosa F. (2014). Raynaud’s phenomenon: from molecular pathogenesis to therapy. Autoimmun. Rev. 2014; 13:655–667.

7. Black CM. Systemic sclerosis ‘state of the art’ 1995. Scand. J. Rheumatol. 1995;24:194–196.

8. Garner R, Kumari R , Lanyon P, Doherty M, Zhang W. Prevalence, risk factors and associations of primary Raynaud’s phenomenon: systematic review and meta-analysis of observational studies. BMJ 2015; Open 5: e006389.

9. Maverakis E, Patel F, Kronenberg DG, Chung L, Fiorentino D, Allanore Y, et al. (2014). International consensus criteria for the diagnosis of Raynaud’s phenomenon. J. Autoimmun. 2014;4:60–65.

10. Fardoun MM, Nassif J, Issa K, Baydoun E, Eid AH. Raynaud’s Phenomenon: A brief review of the underlying mechanisms. Front. Pharmacol. 2016;7:438.

11. Greenstein D, Jeffcote N, Ilsley D, Kester RC. The menstrual cycle and Raynaud’s phenomenon. Angiology. 1996;47:427–436.

12. Wigley FM. Clinical practice. Raynaud’s phenomenon. N. Engl. J. Med. 2002;347:1001–1008.

13. Easter M J, Marshall JM. Contribution of prostanoids to endothelium-dependent vasodilatation in the digital circulation of women with primary Raynaud’s disease. Clin. Sci. (Lond). 2005;109:45–54.

14. Guimaraes S, Moura D. Vascular adrenoceptors: an update. Pharmacol. Rev. 2001;53:319–356.

15. Ahles A, Engelhardt S. Polymorphic variants of adrenoceptors: pharmacology, physiology, and role in disease. Pharmacol. Rev. 2014;66:598–637.

16. McCance KL, Huether SE. Pathophysiology: The Biologic Basis for Disease in Adults and Children. Amsterdam: Elsevier. 2013.

17. Polonia JJ., Paiva MQ, Guimaraes S. Pharmacological characterization of postsynaptic alpha-adrenoceptor subtypes in five different dog arteries in-vitro. J. Pharm. Pharmacol. 1985;37:205–208.

18. Johnson JM, Kellogg DLJr. Local thermal control of the human cutaneous circulation. J. Appl. Physiol. 2010;109:1229–1238.

19. Freedman RR, Sabharwal SC, Moten M, Migaly P. Local temperature modulates alpha 1- and alpha 2-adrenergic vasoconstriction in men. Am. J. Physiol. 1992;263:H1197–H1200.20. MacDonald E, Kobilka BK, Scheinin M. Gene targeting–homing in on alpha2-adrenoceptor-subtype function.Trends Pharmacol. Sci. 1997;18:211–219.

21. Chotani MA, Flavahan S, Mitra S, Daunt D, Flavahan NA. Silent alpha(2C)-adrenergic receptors enable cold-induced vasoconstriction in cutaneous arteries. Am. J. Physiol. Heart Circ. Physiol. 2000;278:H1075–H1083.

22. Sallinen J, Link RE, Haapalinna A, Viitamaa T, Kulatunga M, Sjoholm B, et al. Genetic alteration of alpha 2C-adrenoceptor expression in mice: influence on locomotor, hypothermic, and neurochemical effects of dexmedetomidine, a subtype-nonselective alpha 2-adrenoceptor agonist. Mol. Pharmacol. 1997;51:36–46.

23. Jeyaraj SC, Chotani MA, Mitra S, Gregg HE, Flavahan NA, Morrison KJ. Cooling evokes redistribution of alpha2C-adrenoceptors from Golgi to plasma membrane in transfected human embryonic kidney 293 cells. Mol. Pharmacol. 2001;60:1195–1200.

24. Bailey SR, Eid AH, Mitra S, Flavahan S, Flavahan NA. Rho kinase mediates cold-induced constriction of cutaneous arteries: role of alpha2C-adrenoceptor translocation. Circ. Res. 2004;94:1367–1374.

25. Maricq HR, Carpentier PH, Weinrich MC, Keil JE, Franco A, Drouet P, et al. Geographic variation in the prevalence of Raynaud’s phenomenon: Charleston, SC, USA, vs Tarentaise, Savoie, France. J. Rheumatol. 1993;20:70–76.

26. Belch JJF, Ho M. “Vasospastic disorders and vasculitis,” in Vascular and Endovascular Surgery, eds J. D. Beard and P. A. Gaines (London: WB Saunders and Company). 2001;217–240.

27. Garner R, Kumari R, Lanyon P, Doherty M, Zhang W. Prevalence, risk factors and associations of primary Raynaud’s phenomenon: systematic review and meta-analysis of observational studies. BMJ Open 5. 2015;e006389.

28. Mayes MD. Epidemiologic studies of environmental agents and systemic autoimmune diseases. Environ. Health Perspect. 1999;107(Suppl. 5):743–748.

29. Fraenkel L, Zhang Y, Chaisson CE, Evans SR, Wilson PW, Felson DT. The association of estrogen replacement therapy and the Raynaud phenomenon in postmenopausal women. Ann. Intern. Med. 1998;129:208–211.

30. Chan NN, MacAllister RJ, Colhoun HM, Vallance P, Hingorani AD. Changes in endothelium-dependent vasodilatation and alpha- adrenergic responses in resistance vessels during the menstrual cycle in healthy women. J. Clin. Endocrinol. Metab. 2001;86:2499–2504.

31. Li T, Xiao X, Zhang J, Zhu Y, Hu Y, Zang J, et al. Age and sex differences in vascular responsiveness in healthy and trauma patients: contribution of estrogen receptor-mediated Rho kinase and PKC pathways. Am. J. Physiol. Heart Circ. Physiol. 2014;306:H1105–H1115.

32. Charkoudian N, Stachenfeld N. Sex hormone effects on autonomic mechanisms of thermoregulation in humans. Auton. Neurosci. 2016;196:75–80.

33. Flavahan, N. A. A vascular mechanistic approach to understanding Raynaud phenomenon. Nat. Rev. Rheumatol. 2015;11:146–158.

34. English KM, Jones RD, Jones TH, Morice AH, Channer KS. Gender differences in the vasomotor effects of different steroid hormones in rat pulmonary and coronary arteries. Horm. Metab. Res. 2001;33:645–652.

35. Eid AH, Maiti K, Mitra S, Chotani MA, Flavahan S, Bailey SR, et al. Estrogen increases smooth muscle expression of alpha2C-adrenoceptors and cold-induced constriction of cutaneous arteries. Am. J. Physiol. Heart Circ. Physiol. 2007;293:H1955–H1961.

36. Tan FK, Arnett FC. Genetic factors in the etiology of systemic sclerosis and Raynaud phenomenon. Curr. Opin. Rheumatol. 2000;12:511–519.

37. Susol E, MacGregor AJ, Barrett JH, Wilson H, Black C, Welsh K, et al. A two-stage, genome-wide screen for susceptibility loci in primary Raynaud’s phenomenon. Arthritis Rheum. 2000;43:1641–1646.

38. Pistorius MA, Planchon B, Schott JJ, Lemarec H. [Heredity and genetic aspects of Raynaud’s disease]. J. Mal. Vasc. 2006;31:10–15.

39. Sharathkumar AA, Castillo-Caro P. Primary Raynaud’s phenomenon in an infant: a case report and review of literature. Pediatr. Rheumatol. Online J. 2011;9:16.

40. Fontana L, Marion MJ, Ughetto S, Catilina P. Glutathione S-transferase M1 and GST T1 genetic polymorphisms and Raynaud’s phenomenon in French vinyl chloride monomer-exposed workers. J. Hum. Genet. 2006;51:879–886.