Author + information
- Received June 13, 2018
- Revision received August 29, 2018
- Accepted August 30, 2018
- Published online December 31, 2018.
- Zhen Li, BSa,b,
- Chelsea L. Organ, PhDa,b,
- Jianming Kang, PhDc,
- David J. Polhemus, PhDa,b,
- Rishi K. Trivedi, PhDa,b,
- Thomas E. Sharp III, PhDa,
- Jack S. Jenkinsa,
- Ya-xiong Tao, PhDd,
- Ming Xian, PhDc and
- David J. Lefer, PhDa,b,∗ ()
- aCardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, Louisiana
- bDepartment of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana
- cDepartment of Chemistry, Washington State University, Pullman, Washington
- dDepartment of Anatomy, Physiology, and Pharmacology, Auburn University College of Veterinary Medicine, Auburn, Alabama
- ↵∗Address for correspondence:
Dr. David J. Lefer, Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, 533 Bolivar Street, Room 408, New Orleans, Louisiana 70112.
• Pressure overload induced by transverse aortic constriction led to severe heart failure accompanied by renal fibrosis and dysfunction, endothelial dysfunction, and exercise intolerance in mice.
• 3-week but not 10-week-delayed H2S therapy preserved left ventricular ejection fraction and attenuated cardiac fibrosis.
• H2S therapy attenuated renal fibrosis and dysfunction, preserved endothelium, and enhanced treadmill exercise capacity.
• H2S therapy blunted the maladaptive overactivation of the sympathetic nervous system, resulting in reduced renal tissue norepinephrine levels as well as attenuated circulating levels of renin, angiotensin II, and aldosterone.
Cardioprotective effects of H2S have been well documented. However, the lack of evidence supporting the benefits afforded by delayed H2S therapy warrants further investigation. Using a murine model of transverse aortic constriction-induced heart failure, this study showed that delayed H2S therapy protects multiple organs including the heart, kidney, and blood-vessel; reduces oxidative stress; attenuates renal sympathetic and renin-angiotensin-aldosterone system pathological activation; and ultimately improves exercise capacity. These findings provide further insights into H2S-mediated cardiovascular protection and implicate the benefits of using H2S-based therapies clinically for the treatment of heart failure.
Supported by National Heart, Lung, and Blood Institute/National Institutes of Health grants 5R01HL092141, 5R01HL093579, and 1U24 HL094373 to Dr. Lefer; and grant 1R01HL116571 to Drs. Xian and Lefer. Funding was also received from the Louisiana State University Medical School Foundation and LSU Medical School Alumni Association. All authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received June 13, 2018.
- Revision received August 29, 2018.
- Accepted August 30, 2018.
- 2018 The Authors