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Sexually dimorphic effects of SARM1 deletion on cardiac NAD + metabolism and function
Nicotinamide adenine dinucleotide (NAD ) decline is repeatedly observed in heart disease and its risk factors. Although strategies promoting NAD synthesis to elevate NAD levels improve cardiac function, whether inhibition of NAD consumption can be therapeutic is less investigated. In this study, we...
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Published in: | American journal of physiology. Heart and circulatory physiology 2022-10, Vol.323 (4), p.H774-H781 |
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Main Authors: | , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Nicotinamide adenine dinucleotide (NAD
) decline is repeatedly observed in heart disease and its risk factors. Although strategies promoting NAD
synthesis to elevate NAD
levels improve cardiac function, whether inhibition of NAD
consumption can be therapeutic is less investigated. In this study, we examined the role of sterile-α and TIR motif containing 1 (SARM1) NAD
hydrolase in mouse hearts, using global SARM1-knockout mice (KO). Cardiac function was assessed by echocardiography in male and female KO mice and wild-type (WT) controls. Hearts were collected for biochemical, histological, and molecular analyses. We found that the cardiac NAD
pool was elevated in female KO mice, but only trended to increase in male KO mice. SARM1 deletion induced changes to a greater number of NAD
metabolism transcripts in male mice than in female mice. Body weights, cardiac systolic and diastolic function, and geometry showed no changes in both male and female KO mice compared with WT counterparts. Male KO mice showed a small, but significant, elevation in cardiac collagen levels compared with WT counterparts, but no difference in collagen levels was detected in female mice. The increased collagen levels were associated with greater number of altered profibrotic and senescence-associated inflammatory genes in male KO mice, but not in female KO mice.
We examined the effects of SARM1 deletion on NAD
pool, transcripts of NAD
metabolism, and fibrotic pathway for the first time in mouse hearts. We observed the sexually dimorphic effects of SARM1 deletion. How these sex-dependent effects influence the outcomes of SARM1 deficiency in male and female mice in responses to cardiac stresses warrant further investigation. The elevation of cardiac NAD
pool by SARM1 deletion provides evidence that targeting SARM1 may reverse disease-related NAD
decline. |
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ISSN: | 0363-6135 1522-1539 |
DOI: | 10.1152/ajpheart.00370.2022 |