Early and late effects of the DPP-4 inhibitor vildagliptin in a rat model of post-myocardial infarction heart failure
<p>Abstract</p> <p>Background</p> <p>Progressive remodeling after myocardial infarction (MI) is a leading cause of morbidity and mortality. Recently, glucagon-like peptide (GLP)-1 was shown to have cardioprotective effects, but treatment with GLP-1 is limited by its sho...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2011-09-01
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| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | http://www.cardiab.com/content/10/1/85 |
| _version_ | 1811276695696572416 |
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| author | van Gilst Wiek H Meissner Maxi Silljé Herman HW Yin Meimei de Boer Rudolf A |
| author_facet | van Gilst Wiek H Meissner Maxi Silljé Herman HW Yin Meimei de Boer Rudolf A |
| author_sort | van Gilst Wiek H |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Progressive remodeling after myocardial infarction (MI) is a leading cause of morbidity and mortality. Recently, glucagon-like peptide (GLP)-1 was shown to have cardioprotective effects, but treatment with GLP-1 is limited by its short half-life. It is rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4), an enzyme which inhibits GLP-1 activity. We hypothesized that the DPP-4 inhibitor vildagliptin will increase levels of GLP-1 and may exert protective effects on cardiac function after MI.</p> <p>Methods</p> <p>Sprague-Dawley rats were either subjected to coronary ligation to induce MI and left ventricular (LV) remodeling, or sham operation. Parts of the rats with an MI were pre-treated for 2 days with the DPP-4 inhibitor vildagliptin (MI-Vildagliptin immediate, MI-VI, 15 mg/kg/day). The remainder of the rats was, three weeks after coronary artery ligation, subjected to treatment with DPP-4 inhibitor vildagliptin (MI-Vildagliptin Late, MI-VL) or control (MI). At 12 weeks, echocardiography and invasive hemodynamics were measured and molecular analysis and immunohistochemistry were performed.</p> <p>Results</p> <p>Vildagliptin inhibited the DPP-4 enzymatic activity by almost 70% and increased active GLP-1 levels by about 3-fold in plasma in both treated groups (p < 0.05 vs. non-treated groups). Cardiac function (ejection fraction) was decreased in all 3 MI groups compared with Sham group (p < 0.05); treatment with vildagliptin, either early or late, did not reverse cardiac remodeling. ANP (atrial natriuretic peptide) and BNP (brain natriuretic peptide) mRNA levels were significantly increased in all 3 MI groups, but no significant reductions were observed in both vildagliptin groups. Vildagliptin also did not change cardiomyocyte size or capillary density after MI. No effects were detected on glucose level and body weight in the post-MI remodeling model.</p> <p>Conclusion</p> <p>Vildagliptin increases the active GLP-1 level via inhibition of DPP-4, but it has no substantial protective effects on cardiac function in this well established long-term post-MI cardiac remodeling model.</p> |
| first_indexed | 2024-04-13T00:01:19Z |
| format | Article |
| id | doaj.art-5c67da43770444e2b3496dfb9a3cf074 |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-04-13T00:01:19Z |
| publishDate | 2011-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-5c67da43770444e2b3496dfb9a3cf0742022-12-22T03:11:20ZengBMCCardiovascular Diabetology1475-28402011-09-011018510.1186/1475-2840-10-85Early and late effects of the DPP-4 inhibitor vildagliptin in a rat model of post-myocardial infarction heart failurevan Gilst Wiek HMeissner MaxiSilljé Herman HWYin Meimeide Boer Rudolf A<p>Abstract</p> <p>Background</p> <p>Progressive remodeling after myocardial infarction (MI) is a leading cause of morbidity and mortality. Recently, glucagon-like peptide (GLP)-1 was shown to have cardioprotective effects, but treatment with GLP-1 is limited by its short half-life. It is rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4), an enzyme which inhibits GLP-1 activity. We hypothesized that the DPP-4 inhibitor vildagliptin will increase levels of GLP-1 and may exert protective effects on cardiac function after MI.</p> <p>Methods</p> <p>Sprague-Dawley rats were either subjected to coronary ligation to induce MI and left ventricular (LV) remodeling, or sham operation. Parts of the rats with an MI were pre-treated for 2 days with the DPP-4 inhibitor vildagliptin (MI-Vildagliptin immediate, MI-VI, 15 mg/kg/day). The remainder of the rats was, three weeks after coronary artery ligation, subjected to treatment with DPP-4 inhibitor vildagliptin (MI-Vildagliptin Late, MI-VL) or control (MI). At 12 weeks, echocardiography and invasive hemodynamics were measured and molecular analysis and immunohistochemistry were performed.</p> <p>Results</p> <p>Vildagliptin inhibited the DPP-4 enzymatic activity by almost 70% and increased active GLP-1 levels by about 3-fold in plasma in both treated groups (p < 0.05 vs. non-treated groups). Cardiac function (ejection fraction) was decreased in all 3 MI groups compared with Sham group (p < 0.05); treatment with vildagliptin, either early or late, did not reverse cardiac remodeling. ANP (atrial natriuretic peptide) and BNP (brain natriuretic peptide) mRNA levels were significantly increased in all 3 MI groups, but no significant reductions were observed in both vildagliptin groups. Vildagliptin also did not change cardiomyocyte size or capillary density after MI. No effects were detected on glucose level and body weight in the post-MI remodeling model.</p> <p>Conclusion</p> <p>Vildagliptin increases the active GLP-1 level via inhibition of DPP-4, but it has no substantial protective effects on cardiac function in this well established long-term post-MI cardiac remodeling model.</p>http://www.cardiab.com/content/10/1/85vildagliptinmyocardial infarctioncardiac remodelingheart failurediabetes |
| spellingShingle | van Gilst Wiek H Meissner Maxi Silljé Herman HW Yin Meimei de Boer Rudolf A Early and late effects of the DPP-4 inhibitor vildagliptin in a rat model of post-myocardial infarction heart failure Cardiovascular Diabetology vildagliptin myocardial infarction cardiac remodeling heart failure diabetes |
| title | Early and late effects of the DPP-4 inhibitor vildagliptin in a rat model of post-myocardial infarction heart failure |
| title_full | Early and late effects of the DPP-4 inhibitor vildagliptin in a rat model of post-myocardial infarction heart failure |
| title_fullStr | Early and late effects of the DPP-4 inhibitor vildagliptin in a rat model of post-myocardial infarction heart failure |
| title_full_unstemmed | Early and late effects of the DPP-4 inhibitor vildagliptin in a rat model of post-myocardial infarction heart failure |
| title_short | Early and late effects of the DPP-4 inhibitor vildagliptin in a rat model of post-myocardial infarction heart failure |
| title_sort | early and late effects of the dpp 4 inhibitor vildagliptin in a rat model of post myocardial infarction heart failure |
| topic | vildagliptin myocardial infarction cardiac remodeling heart failure diabetes |
| url | http://www.cardiab.com/content/10/1/85 |
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