Haptoglobin genotype is a determinant of survival and cardiac remodeling after myocardial infarction in diabetic mice Export

@article{citeulike:4746392, abstract = {Background:\&\#10;We have recently demonstrated in man that a functional allelic polymorphism in the Haptoglobin (Hp) gene plays a major role in determining survival and congestive heart failure after myocardial infarction (MI). We sought to recapitulate the effect of Hp type on outcomes and cardiac remodeling after MI in transgenic mice.\&\#10;Methods:\&\#10;The Hp 2 allele exists only in man. Wild type C57Bl/6 mice carry the Hp 1 allele with high homology to the human Hp 1 allele. We genetically engineered a murine Hp 2 allele and targeted its insertion by homologous recombination to the murine Hp locus to create Hp 2 mice. Diabetes Mellitus (DM) was induced with streptozotocin. MI was produced by occlusion of the left anterior descending artery in DM C57Bl/6 mice carrying the Hp 1 or Hp 2 allele. MI size was determined with TTC staining. Left ventricular (LV) function and dimensions were assessed by 2-dimensional echocardiography.\&\#10;Results:\&\#10;In the absence of DM, Hp 1-1 and Hp 2-2 mice had similar LV dimensions and LV function. MI size was similar in DM Hp 1-1 and 2-2 mice 24 hours after MI (50.2+/-2.1\%and 46.9+/-5.5\%, respectively, p=0.6). However, DM Hp 1-1 mice had a significantly lower mortality rate than DM Hp 2-2 mice 30 days after MI (HR 0.41, 95\% CI (0.19-0.95), p=0.037 by log rank). LV chamber dimensions were significantly increased in DM Hp 2-2 mice compared to DM Hp 1-1 mice 30 days after MI (0.196+/-0.01 cm^2 vs. 0.163+/-0.01 cm^2, respectively; p=0.029).\&\#10;Conclusion:\&\#10;In DM mice the Hp 2-2 genotype is associated with increased mortality and more severe cardiac remodeling 30 days after MI.}, author = {Asaf, Roy and Blum, Shany and Roguin, Ariel and Kalet-Litman, Shiri and Kheir, Jad and Frisch, Avi and Miller-Lotan, Rachel and Levy, Andrew}, citeulike-article-id = {4746392}, citeulike-linkout-0 = {http://dx.doi.org/10.1186/1475-2840-8-29}, doi = {10.1186/1475-2840-8-29}, issn = {1475-2840}, journal = {Cardiovascular Diabetology}, month = {June}, pages = {29+}, posted-at = {2009-06-04 17:40:23}, title = {Haptoglobin genotype is a determinant of survival and cardiac remodeling after myocardial infarction in diabetic mice}, url = {http://dx.doi.org/10.1186/1475-2840-8-29}, volume = {8}, year = {2009} }

TY - JOUR ID - citeulike:4746392 L3 - citeulike-article-id:4746392 N2 - Background:
We have recently demonstrated in man that a functional allelic polymorphism in the Haptoglobin (Hp) gene plays a major role in determining survival and congestive heart failure after myocardial infarction (MI). We sought to recapitulate the effect of Hp type on outcomes and cardiac remodeling after MI in transgenic mice.
Methods:
The Hp 2 allele exists only in man. Wild type C57Bl/6 mice carry the Hp 1 allele with high homology to the human Hp 1 allele. We genetically engineered a murine Hp 2 allele and targeted its insertion by homologous recombination to the murine Hp locus to create Hp 2 mice. Diabetes Mellitus (DM) was induced with streptozotocin. MI was produced by occlusion of the left anterior descending artery in DM C57Bl/6 mice carrying the Hp 1 or Hp 2 allele. MI size was determined with TTC staining. Left ventricular (LV) function and dimensions were assessed by 2-dimensional echocardiography.
Results:
In the absence of DM, Hp 1-1 and Hp 2-2 mice had similar LV dimensions and LV function. MI size was similar in DM Hp 1-1 and 2-2 mice 24 hours after MI (50.2+/-2.1%and 46.9+/-5.5%, respectively, p=0.6). However, DM Hp 1-1 mice had a significantly lower mortality rate than DM Hp 2-2 mice 30 days after MI (HR 0.41, 95% CI (0.19-0.95), p=0.037 by log rank). LV chamber dimensions were significantly increased in DM Hp 2-2 mice compared to DM Hp 1-1 mice 30 days after MI (0.196+/-0.01 cm^2 vs. 0.163+/-0.01 cm^2, respectively; p=0.029).
Conclusion:
In DM mice the Hp 2-2 genotype is associated with increased mortality and more severe cardiac remodeling 30 days after MI. JF - Cardiovascular Diabetology SN - 1475-2840 TI - Haptoglobin genotype is a determinant of survival and cardiac remodeling after myocardial infarction in diabetic mice VL - 8 SP - 29 AU - Asaf, Roy AU - Blum, Shany AU - Roguin, Ariel AU - Kalet-Litman, Shiri AU - Kheir, Jad AU - Frisch, Avi AU - Miller-Lotan, Rachel AU - Levy, Andrew PY - 2009/06/02/ UR - http://dx.doi.org/10.1186/1475-2840-8-29 ER -