Hydrogen sulfide prevents arterial medial calcification in rats with diabetic nephropathy.

Abstract

BACKGROUND:

Arterial medial calcification (AMC) is associated with a high incidence of cardiovascular risk in patients with type 2 diabetes and chronic kidney disease. Here, we tested whether hydrogen sulfide (H2S) can prevent AMC in rats with diabetic nephropathy (DN).

METHODS:

DN was induced by a single injection of streptozotocin and high-fat diet (45% kcal as fat) containing 0.75% adenine in Sprague-Dawley rats for 8 weeks.

RESULTS:

Rats with DN displayed obvious calcification in aorta, and this was significantly alleviated by Sodium Hydrosulfide (NaHS, a H2S donor, 50 μmol/kg/day for 8 weeks) treatment through decreasing calcium and phosphorus content, ALP activity and calcium deposition in aorta. Interestingly, the main endogenous H2S generating enzyme activity and protein expression of cystathionine-γ-lyase (CSE) were largely reduced in the arterial wall of DN rats. Exogenous NaHS treatment restored CSE activity and its expression, inhibited aortic osteogenic transformation by upregulating phenotypic markers of smooth muscle cells SMα-actin and SM22α, and downregulating core binding factor α-1 (Cbfα-1, a key factor for bone formation), protein expressions in rats with DN when compared to the control group. NaHS administration also significantly reduced Stat3 activation, cathepsin S (CAS) activity and TGF-β1 protein level, and improved aortic elastin expression.

CONCLUSIONS:

H2S may have a clinical significance for treating AMC in people with DN by reducing Stat3 activation, CAS activity, TGF-β1 level and increasing local elastin level.

• Authors: Fang-Zheng Wang, Hong Zhou, Hong-Yu Wang, Hang-Bing Dai, Qing Gao, Pei Qian, Ye-Bo Zhou
• Journal: BMC cardiovascular disorders (BMC Cardiovasc Disord) Vol. 21 Issue 1 Pg. 495 (10 13 2021) ISSN: 1471-2261 [Electronic] England
• PMID: 34645391 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• STAT3 Transcription Factor
• Stat3 protein, rat
• Tgfb1 protein, rat
• Transforming Growth Factor beta1
• Elastin
• Cathepsins
• cathepsin S
• Hydrogen Sulfide

Topics

• Animals
• Aorta (drug effects, metabolism, pathology)
• Aortic Diseases (etiology, metabolism, pathology, prevention & control)
• Cathepsins (metabolism)
• Diabetic Nephropathies (complications, drug therapy, metabolism)
• Disease Models, Animal
• Elastin (metabolism)
• Hydrogen Sulfide (pharmacology)
• Male
• Rats, Sprague-Dawley
• STAT3 Transcription Factor (metabolism)
• Transforming Growth Factor beta1 (metabolism)
• Tunica Media (drug effects, metabolism, pathology)
• Vascular Calcification (etiology, metabolism, pathology, prevention & control)
• Rats