| First Author | Bai W | Year | 2024 |
| Journal | EMBO Rep | Volume | 25 |
| Issue | 1 | Pages | 128-143 |
| PubMed ID | 38177907 | Mgi Jnum | J:360542 |
| Mgi Id | MGI:7609942 | Doi | 10.1038/s44319-023-00015-3 |
| Citation | Bai W, et al. (2024) S-nitrosylation of AMPKgamma impairs coronary collateral circulation and disrupts VSMC reprogramming. EMBO Rep 25(1):128-143 |
| abstractText | Collateral circulation is essential for blood resupply to the ischemic heart, which is dictated by the contractile phenotypic restoration of vascular smooth muscle cells (VSMC). Here we investigate whether S-nitrosylation of AMP-activated protein kinase (AMPK), a key regulator of the VSMC phenotype, impairs collateral circulation. In rats with collateral growth and development, nitroglycerin decreases coronary collateral blood flow (CCBF), inhibits vascular contractile phenotypic restoration, and increases myocardial infarct size, accompanied by reduced AMPK activity in the collateral zone. Nitric oxide (NO) S-nitrosylates human recombinant AMPKgamma1 at cysteine 131 and decreases AMP sensitivity of AMPK. In VSMCs, exogenous expression of S-nitrosylation-resistant AMPKgamma1 or deficient NO synthase (iNOS) prevents the disruption of VSMC reprogramming. Finally, hyperhomocysteinemia or hyperglycemia increases AMPKgamma1 S-nitrosylation, prevents vascular contractile phenotypic restoration, reduces CCBF, and increases the infarct size of the heart in Apoe(-/-) mice, all of which is rescued in Apoe(-/-)/iNOS(sm-/-) mice or Apoe(-/-) mice with enforced expression of the AMPKgamma1-C130A mutant following RI/MI. We conclude that nitrosative stress disrupts coronary collateral circulation during hyperhomocysteinemia or hyperglycemia through AMPK S-nitrosylation. |
