Display options
Cite
Kashyap S, Engel S, Osman M, et al. Cardiovascular manifestations of renovascular hypertension in diabetic mice. PeerJ. 2016;4:e1736doi: 10.7717/peerj.1736.
Kashyap, S., Engel, S., Osman, M., Al-Saiegh, Y., Wongjarupong, A., & Grande, J. P. (2016). Cardiovascular manifestations of renovascular hypertension in diabetic mice. PeerJ, 4e1736. https://doi.org/10.7717/peerj.1736
Kashyap, Sonu, et al. "Cardiovascular manifestations of renovascular hypertension in diabetic mice." PeerJ vol. 4 (2016): e1736. doi: https://doi.org/10.7717/peerj.1736
Kashyap S, Engel S, Osman M, Al-Saiegh Y, Wongjarupong A, Grande JP. Cardiovascular manifestations of renovascular hypertension in diabetic mice. PeerJ. 2016 Feb 22;4:e1736. doi: 10.7717/peerj.1736. eCollection 2016. PMID: 26925344; PMCID: PMC4768709.
Copy Download .nbib Format: NLM
Share it on

PeerJ. 2016 Feb 22;4:e1736. doi: 10.7717/peerj.1736. eCollection 2016.

Cardiovascular manifestations of renovascular hypertension in diabetic mice.

PeerJ

Sonu Kashyap, Sean Engel, Mazen Osman, Yousif Al-Saiegh, Asarn Wongjarupong, Joseph P Grande

Affiliations

  1. Department of Laboratory Medicine and Pathology, Mayo Clinic , Rochester, MN , USA.
  2. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA; Wartburg College, Waverly, IA, United States.
  3. Hannover Medical School (MHH) , Hannover , Germany.
  4. Department of Medicine, Chulalongkorn University , Bangkok , Thailand.
  5. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.

PMID: 26925344 PMCID: PMC4768709 DOI: 10.7717/peerj.1736

Abstract

Purpose. Type 2 diabetes is the leading cause of end stage renal disease in the United States. Atherosclerotic renal artery stenosis is commonly observed in diabetic patients and impacts the rate of renal and cardiovascular disease progression. We sought to test the hypothesis that renovascular hypertension, induced by unilateral renal artery stenosis, exacerbates cardiac remodeling in leptin-deficient (db/db) mice, which serves as a model of human type II diabetes. Methods. We employed a murine model of renovascular hypertension through placement of a polytetrafluoroethylene cuff on the right renal artery in db/db mice. We studied 109 wild-type (non-diabetic, WT) and 95 db/db mice subjected to renal artery stenosis (RAS) or sham surgery studied at 1, 2, 4, and 6+ weeks following surgery. Cardiac remodeling was assessed by quantitative analysis of the percent of myocardial surface area occupied by interstitial fibrosis tissue, as delineated by trichrome stained slides. Aortic pathology was assessed by histologic sampling of grossly apparent structural abnormalities or by section of ascending aorta of vessels without apparent abnormalities. Results. We noted an increased mortality in db/db mice subjected to RAS. The mortality rate of db/db RAS mice was about 23.5%, whereas the mortality rate of WT RAS mice was only 1.5%. Over 60% of mortality in the db/db mice occurred in the first two weeks following RAS surgery. Necropsy showed massive intrathoracic hemorrhage associated with aortic dissection, predominantly in the ascending aorta and proximal descending aorta. Aortas from db/db RAS mice showed more smooth muscle dropout, loss of alpha smooth muscle actin expression, medial disruption, and hemorrhage than aortas from WT mice with RAS. Cardiac tissue from db/db RAS mice had more fibrosis than did cardiac tissue from WT RAS mice. Conclusions. db/db mice subjected to RAS are prone to develop fatal aortic dissection, which is not observed in WT mice with RAS. The db/db RAS model provides the basis for future studies directed towards defining basic mechanisms underlying the interaction of hypertension and diabetes on the development of aortic lesions.

Keywords: Cardiovascular disease; Diabetes; Hypertension; Renal artery stenosis

References

  1. Am J Med. 2003 Jul;115(1):41-6 - PubMed
  2. J Diabetes Complications. 2015 Nov-Dec;29(8):1330-6 - PubMed
  3. Am J Med. 2000 Dec 1;109 (8):642-7 - PubMed
  4. N Engl J Med. 2006 Aug 24;355(8):788-98 - PubMed
  5. Nephrol Dial Transplant. 2010 Nov;25(11):3615-22 - PubMed
  6. Clin Sci (Lond). 2010 Mar 09;118(11):681-9 - PubMed
  7. J Am Heart Assoc. 2013 Jun 19;2(3):e000269 - PubMed
  8. Eur Heart J. 2013 Oct;34(39):3035-87 - PubMed
  9. Expert Rev Cardiovasc Ther. 2015 Dec;13(12):1289-90 - PubMed
  10. Diabetes Care. 2000 Apr;23(4):539-43 - PubMed
  11. Eur Heart J. 2002 Nov;23(21):1684-91 - PubMed
  12. World J Cardiol. 2014 Aug 26;6(8):855-60 - PubMed
  13. Exp Biol Med (Maywood). 2002 Dec;227(11):943-56 - PubMed
  14. J Am Soc Hypertens. 2014 Apr;8(4):254-61 - PubMed
  15. Circ Res. 2011 Sep 2;109(6):680-6 - PubMed
  16. Circ Res. 1984 Mar;54(3):286-93 - PubMed
  17. BMC Nephrol. 2014 Apr 04;15:58 - PubMed
  18. J Prev Med Public Health. 2014 Jul;47(4):216-29 - PubMed
  19. J Am Coll Cardiol. 2006 Feb 21;47(4):693-700 - PubMed
  20. Nephrologie. 1998;19(7):403-10 - PubMed
  21. J Vis Exp. 2012 Apr 16;(62):null - PubMed
  22. Angiology. 2016 Jul;67(6):513-25 - PubMed
  23. Circulation. 1996 Mar 15;93(6):1148-54 - PubMed
  24. N Engl J Med. 2001 Feb 8;344(6):431-42 - PubMed
  25. Circ Heart Fail. 2015 Jul;8(4):788-98 - PubMed
  26. Circ Res. 1991 Apr;68(4):905-21 - PubMed
  27. Curr Opin Pharmacol. 2010 Apr;10(2):203-7 - PubMed
  28. Diabetes Care. 2014 Oct;37(10):2864-83 - PubMed
  29. Am J Physiol Renal Physiol. 2009 Oct;297(4):F1055-68 - PubMed
  30. Angiology. 2016 Jul;67(6):510-2 - PubMed
  31. J Renal Inj Prev. 2015 Jun 01;4(2):28-33 - PubMed
  32. Circulation. 1998 Jul 7;98(1):73-81 - PubMed
  33. Am J Physiol Renal Physiol. 2013 Apr 1;304(7):F938-47 - PubMed
  34. J Vasc Surg. 2002 Sep;36(3):443-51 - PubMed
  35. Am J Physiol Renal Physiol. 2012 Jun 1;302(11):F1455-64 - PubMed

Publication Types

Grant support