Modulation of Vascular ACE by Oxidative Stress in Young Syrian Cardiomyopathic Hamsters: Therapeutic Implications

Overview

Journal J Clin Med

Specialty General Medicine

Date 2016 Jul 16

PMID 27420103

Citations 2

Authors

Nildris Cruz

Jorge D Miranda

Maria J Crespo

Affiliations

Soon will be listed here.

Abstract

Increased vascular angiotensin-converting enzyme (ACE) activity and oxidative stress are present in young Syrian cardiomyopathic hamsters (SCH) before the clinical manifestation of heart failure (HF). The developmental time-course of these alterations and their potential interactions, however, are still unknown. We evaluated mRNA and protein levels of ACE, endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS) in the vasculature of SCH from one to four months of age. Total RNA and proteins were quantified with real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot, respectively. The role of nitric oxide (NO) on vascular ACE activity was also assessed. ACE mRNA and protein levels were up-regulated in SCH at two months of age compared with controls (CT) (p < 0.05). At this two-month stage, eNOS protein levels were lower in SCH (87%) than in CT (100%) (p < 0.05), although iNOS protein levels increased significantly (482%) compared to CT (100%; p < 0.05). In addition, ACE mRNA expression and activity were modulated by NO at two months of age. Thus, the combination of low eNOS and high iNOS protein levels may underlie vascular renin-angiotensin system (RAS) over-activation. Altogether, these factors may contribute to the development of endothelial dysfunction and vascular hyper-reactivity in the early stages of heart failure, and eventually trigger cardiac deterioration in this animal model of HF.

Citing Articles

Oral Supplementation with Betaine Powder Ameliorated High Blood Pressure in Spontaneously Hypertensive Rats.

Pelpolage S, Sasaki R, Shimada K, Nagura T, Uchino H, Han K Metabolites. 2024; 14(7).

PMID: 39057713 PMC: 11279126. DOI: 10.3390/metabo14070390.

Human Tissue Angiotensin Converting Enzyme (ACE) Activity Is Regulated by Genetic Polymorphisms, Posttranslational Modifications, Endogenous Inhibitors and Secretion in the Serum, Lungs and Heart.

Banhegyi V, Enyedi A, Fulop G, Olah A, Siket I, Varadi C Cells. 2021; 10(7).

PMID: 34359878 PMC: 8305685. DOI: 10.3390/cells10071708.

References

Santiago J, Rosas O, Torrado A, Gonzalez M, Kalyan-Masih P, Miranda J . Molecular, anatomical, physiological, and behavioral studies of rats treated with buprenorphine after spinal cord injury. J Neurotrauma. 2009; 26(10):1783-93. PMC: 2864459. DOI: 10.1089/neu.2007.0502. View

Comini L, Bachetti T, Gaia G, Pasini E, Agnoletti L, Pepi P . Aorta and skeletal muscle NO synthase expression in experimental heart failure. J Mol Cell Cardiol. 1996; 28(11):2241-8. DOI: 10.1006/jmcc.1996.0216. View

Umar S, van der Laarse A . Nitric oxide and nitric oxide synthase isoforms in the normal, hypertrophic, and failing heart. Mol Cell Biochem. 2009; 333(1-2):191-201. DOI: 10.1007/s11010-009-0219-x. View

Crespo M, Cruz N, Altieri P, Escobales N . Enalapril and losartan are more effective than carvedilol in preventing dilated cardiomyopathy in the Syrian cardiomyopathic hamster. J Cardiovasc Pharmacol Ther. 2008; 13(3):199-206. DOI: 10.1177/1074248408320006. View

Coral-Vazquez R, Cohn R, Moore S, Hill J, Weiss R, Davisson R . Disruption of the sarcoglycan-sarcospan complex in vascular smooth muscle: a novel mechanism for cardiomyopathy and muscular dystrophy. Cell. 1999; 98(4):465-74. DOI: 10.1016/s0092-8674(00)81975-3. View

Vogel C, Marcotte E . Insights into the regulation of protein abundance from proteomic and transcriptomic analyses. Nat Rev Genet. 2012; 13(4):227-32. PMC: 3654667. DOI: 10.1038/nrg3185. View

Vogel C, de Sousa Abreu R, Ko D, Le S, Shapiro B, Burns S . Sequence signatures and mRNA concentration can explain two-thirds of protein abundance variation in a human cell line. Mol Syst Biol. 2010; 6:400. PMC: 2947365. DOI: 10.1038/msb.2010.59. View

Ferrari R, Guardigli G, Ceconi C . Secondary prevention of CAD with ACE inhibitors: a struggle between life and death of the endothelium. Cardiovasc Drugs Ther. 2010; 24(4):331-9. DOI: 10.1007/s10557-010-6244-x. View

JASMIN G, Bajusz E . Prevention of myocardial generation in hamsters with hereditary cardiomyopathy. Recent Adv Stud Cardiac Struct Metab. 1975; 6:219-29. View

10.

Crespo M, Cruz N, Altieri P, Escobales N . Chronic treatment with N-acetylcysteine improves cardiac function but does not prevent progression of cardiomyopathy in Syrian cardiomyopathic hamsters. J Cardiovasc Pharmacol Ther. 2010; 16(2):197-204. DOI: 10.1177/1074248410387281. View

11.

Silva W, Maldonado H, Velazquez G, Rubio-Davila M, Miranda J, Aquino E . Caveolin isoform expression during differentiation of C6 glioma cells. Int J Dev Neurosci. 2005; 23(7):599-612. DOI: 10.1016/j.ijdevneu.2005.07.007. View

12.

Pacher P, Schulz R, Liaudet L, Szabo C . Nitrosative stress and pharmacological modulation of heart failure. Trends Pharmacol Sci. 2005; 26(6):302-10. PMC: 2228264. DOI: 10.1016/j.tips.2005.04.003. View

13.

Mollnau H, Oelze M, August M, Wendt M, Daiber A, Schulz E . Mechanisms of increased vascular superoxide production in an experimental model of idiopathic dilated cardiomyopathy. Arterioscler Thromb Vasc Biol. 2005; 25(12):2554-9. DOI: 10.1161/01.ATV.0000190673.41925.9B. View

14.

Jessup J, Westwood B, Chappell M, Groban L . Dual ACE-inhibition and AT1 receptor antagonism improves ventricular lusitropy without affecting cardiac fibrosis in the congenic mRen2.Lewis rat. Ther Adv Cardiovasc Dis. 2009; 3(4):245-57. PMC: 2825563. DOI: 10.1177/1753944709338489. View

15.

Cruz-Orengo L, Figueroa J, Torrado A, Puig A, Whittemore S, Miranda J . Reduction of EphA4 receptor expression after spinal cord injury does not induce axonal regeneration or return of tcMMEP response. Neurosci Lett. 2007; 418(1):49-54. PMC: 2570091. DOI: 10.1016/j.neulet.2007.03.015. View

16.

Shaw T, Elliott P, McKenna W . Dilated cardiomyopathy: a genetically heterogeneous disease. Lancet. 2002; 360(9334):654-5. DOI: 10.1016/S0140-6736(02)09879-3. View

17.

Crespo M, Altieri P, Escobales N . Increased vascular angiotensin II binding capacity and ET-1 release in young cardiomyopathic hamsters. Vascul Pharmacol. 2006; 44(4):247-52. DOI: 10.1016/j.vph.2006.01.003. View

18.

Griendling K, Sorescu D, Ushio-Fukai M . NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res. 2000; 86(5):494-501. DOI: 10.1161/01.res.86.5.494. View

19.

Crespo M . Vascular alterations during the development and progression of experimental heart failure. J Card Fail. 1999; 5(1):55-63. DOI: 10.1016/s1071-9164(99)90025-8. View

20.

Crespo M, Altieri P, Escobales N . Altered vascular function in early stages of heart failure in hamsters. J Card Fail. 1998; 3(4):311-8. DOI: 10.1016/s1071-9164(97)90031-2. View