| 000 | 02405 am a22002653u 4500 | ||
|---|---|---|---|
| 042 | _adc | ||
| 100 | 1 | 0 |
_aPotz, Brittany A. _eauthor _9942 |
| 700 | 1 | 0 |
_aSabe, Ashraf A. _eauthor _9943 |
| 700 | 1 | 0 |
_aSabe, Sharif A. _eauthor _9944 |
| 700 | 1 | 0 |
_aLawandy, Isabella J. _eauthor _9945 |
| 700 | 1 | 0 |
_aAbid, M. Ruhul _eauthor _9946 |
| 700 | 1 | 0 |
_aClements, Richard T. _eauthor _9947 |
| 700 | 1 | 0 |
_aSellke, Frank W. _eauthor _9948 |
| 245 | 0 | 0 | _aCalpain Inhibition Decreases Myocardial Fibrosis in Chronically Ischemic Hypercholesterolemic Swine |
| 260 | _c2020-03-29. | ||
| 500 | _a/pmc/articles/PMC7529741/ | ||
| 500 | _a/pubmed/32359903 | ||
| 520 | _aOBJECTIVES: Calpain activation during ischemia is known to play critical roles in myocardial remodeling. We hypothesize that calpain inhibition (CI) may serve to reverse and/or prevent fibrosis in chronically ischemic myocardium. METHODS: Yorkshire swine were fed a high cholesterol diet for 4 weeks followed by placement of an ameroid constrictor on the left circumflex artery to induce myocardial ischemia. 3 weeks later animals received either: no drug, high cholesterol control group (CON; n= 8); low dose CI (0.12 mg/kg; LCI, n= 9); or high dose CI (0.25 mg/kg; HCI, n= 8). The high cholesterol diet and CI were continued for 5 weeks, after which myocardial tissue was harvested. Tissue samples were analyzed by western blot for changes in protein content. RESULTS: In the setting of hypercholesterolemia and chronic myocardial ischemia, CI decreased the expression of collagen in ischemic and non-ischemic myocardial tissue. This reduced collagen content was associated with a corresponding decrease in Jak/STAT/MCP-1 signaling pathway, suggesting a role for Jak 2 signaling in calpain activity. CI also decreases the expression of focal adhesion proteins (vinculin) and stabilizes the expression of cytoskeletal and structural proteins (N-cadherin, α fodrin, desmin, vimentin, filamin, Troponin-I). CI had no significant effect on metabolic and hemodynamic parameters. CONCLUSIONS: Calpain inhibition may be a beneficial medical therapy to decrease collagen formation in patients with coronary artery disease and associated co-morbidities. | ||
| 540 | _a | ||
| 546 | _aen | ||
| 690 | _aArticle | ||
| 655 | 7 |
_aText _2local |
|
| 786 | 0 | _nJ Thorac Cardiovasc Surg | |
| 856 | 4 | 1 |
_uhttp://dx.doi.org/10.1016/j.jtcvs.2019.11.150 _zConnect to this object online. |
| 999 |
_c1708 _d1708 |
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