Molecular Mechanisms of Ischemic Preconditioning with Cardiovascular Aging in Elderly Patients with Arterial Hypertension

E. A. Kartashova, PhD¹; Irina V. Sarvilina, PhD, ScD*²

1Rostov-on-Don State Medical University, Rostov-on-Don, Russian Federation; 2Medical Centre "Novomeditsina", Rostov-on-Don, Russian Federation

*Corresponding author: Irina V. Sarvilina, PhD, ScD. CEO of Medical Centre «Novomeditsina», Rostov-on-Don, Russian Federation..E-mail:

Published: March 16, 2016. DOI: 10.21103/Article6(1)_OA13


The purpose of this study was to analyze molecular mechanisms of ischemic preconditioning (IPC) with cardiovascular aging in elderly patients with isolated systolic hypertension (ISH).

The study included 306 persons divided into two groups: Group 1 (the control group) included 150 elderly patients without AH, and Group 2 (the experimental group) included 156 elderly patients with ISH according to the inclusion/exclusion criteria. The duration of ISH was 13.5 years. All patients received a double combination of antihypertensive drugs. We applied standard methods for identification of ISH and secondary hypertension. Molecular phenotyping of blood plasma with the identification of molecules involved in IPC process were processed with methods of proteomics. The data of the molecular interactions and functional features of proteins were received with STRING 10.0 database. Bioinformatics analysis has revealed the presence of molecules that are the participants in the pathways of IPC, cardiovascular aging and the molecular interactions involved.

ischemic preconditioning; cardiovascular aging; isolated systolic hypertension; proteomics; molecular interactions.
  1. North BJ, Sinclair DA. The intersection between aging and cardiovascular disease. Circ Res. 2012 Apr 13;110(8):1097-108.
  2.  Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises, part I: aging arteries: a “set up” for vascular disease. Circulation. 2003; 107: 139–146.
  3. Lakatta EG, Levy D.  Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises, part II: the aging heart in health: links to heart disease. Circulation. 2003; 107: 346–354.
  4. Nielsen W, Vestbo J, Jensen G. Isolated systolic hypertension (ISH): The most powerful risk factor of stroke and MI. Am J Hypertension. 1995; 8(4):41A.
  5. Boutouyrie P, Tropeano A, Asmar R, Gautier I, Benetos A, Lacolley P, Laurent S. Aortic stiffness is an independent predictor of primary coronary events in hypertensive patients: a longitudinal study. Hypertension.  2002;. 39(1):10-5.
  6. McEniery C, Hall I, Qasem A, Wilkinson I, Cockcroft J. Normal vascular aging: differential effects on wave reflection and aortic pulse wave velocity: the Anglo-Cardiff Collaborative Trial (ACCT) J Am Coll Cardiol. 2005;46(9):1753-60.
  7. Basile J. Hypertension in the elderly: a review of the importance of systolic blood pressure elevation J Clin Hypertens (Greenwich). 2002; 4(2):108–12.
  8. Kearney P, Whelton M, Reynolds K, Muntner P, Whelton P, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005; 365(9455):217–23.
  9. Abete P, Testa G, Cacciatore F, Della-Morte D, Galizia G, Langellotto A,et al. Ischemic preconditioning in the younger and aged heart. Aging Dis. 2011 Apr;2(2):138-48.
  10. Tresch DD, Brady WJ, Aufderheide TP, Lawrence SW, Williams KJ. Comparison of elderly and younger patients with out-of-hospital chest pain. Arch Intern Med. 1996;156:1089–93.
  11. Berger AK, Radford MJ, Wang Y, Krumholz HM. Thrombolytic therapy in older patients. J Am Coll Cardiol. 2000;36:366–74.
  12. Boersma E, Pieper KS, Steyerberg EW, Wilcox RG, Chang WC, Lee KL, et al. Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation. Results from an international trial of 9461 patients The PURSUIT Investigators. Circulation. 2000;101:2557–67.
  13. Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 1986;74:1124-1136.
  14. Kloner RA, Bolli R, Marban E, Reinlib L, Braunwald E. Medical and cellular implications of stunning, hibernation and preconditioning. An NHLBI workshop. Circulation. 1998;97:1848–67.
  15. Napoli C, Pinto A, Cirino G. Pharmacological modulation, preclinical studies, and new clinical features of myocardial ischemic preconditioning. Pharmacol Ther. 2000;88:311–31.
  16. Yellon DM, Downey JM. Preconditioning the myocardium: from cellular physiology to clinical cardiology. Physiol Rev. 2003;83:1113–51.
  17. Kloner RA, Shook T, Przyklenk K et al. Previous angina alters in-hospital outcome in TIMI-4: a clinical correlate to preconditioning? Circulation 1995;91:37-47.
  18. Fenton R, Dickson E, Meyer T, Dobson JGJr. Aging reduces the cardioprotective effect of ischemic preconditioning in rat heart J Mol Cell Cardiol. 2000;32:1371-5.
  19. Bartling B, Friedrich I, Silber RE, Simm A. Ischemic preconditioning is not cardioprotective in senescent human myocardium. Ann Thorac Surg.2003;76:105–11. [PubMed]
  20.  Boengler K, Konietzka I, Buechert A, Heinen Y, Garcia-Dorado D, Heusch G, Schulz R, et al. Loss of ischemic preconditioning’s cardioprotection in aged mouse hearts is associated with reduced gap junctional and mitochondrial levels of connexin 43. Am J Physiol Heart Circ Physiol. 2007;292:H1764–9.
  21. Abete P, Ferrara N, Cacciatore F, Sagnelli E, Manzi M, Carnovale V, et al. Angina-induced protection against myocardial infarction in adult and senescent patients. A loss of preconditioning mechanism in aging heart. J Am Coll Cardiol. 1997;30:947–54.
  22. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Böhm M, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013;34(28):2159-219.
  23. Pajaniappan M, Glober NK, Kennard S, Liu H, Zhao N, Lilly B.Endothelial cells downregulate apolipoprotein D expression in mural cells through paracrine secretion and Notch signaling. Am J Physiol Heart Circ Physiol. 2011; 301(3): H784–H793.
  24. Han D, Zhang C, Fan WJ, Pan WJ, Feng DM, Qu SL, et al. Myocardial ischemic preconditioning upregulated protein 1(Mipu1):zinc finger protein 667 - a multifunctional KRAB/C2H2 zinc finger protein. Braz J Med Biol Res. 2015; 48(1): 1–5.

The fully formatted PDF version is available.

Download Article

Int J Biomed. 2016; 6(1):60-64. © 2016 International Medical Research and Development Corporation. All rights reserved.