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Regional Differences of Gene Expression in Human and Rodent Heart
S28 Journal of Cardiac Failure Vol. 9 No. 5 Suppl. 2003 098
099
Regional Differences of Gene Expression in Human and Rodent Heart Saumya Sharma,1 Peter Razeghi,1 Ali Shakir,1 Brad Keneson,2 Fred Clubb,2 Heinrich Taegtmeyer1—1Cardiology, University of Texas Houston Medical School, Houston, TX; 2Pathology, Texas Heart Institute, Houston, TX
Left Ventricular End-Diastolic Dimension Correlates with Absence of Inotropic Contractile Reserve in Patients with Nonischemic Cardiomyopathy Ramzan M. Zakir,1 Marcin Kowalski,1 Reza Mohammadi,1 Siu-Sun Yao,1 Farooq A. Chaudhry1—1Cardiology, St.Luke’s-Roosevelt Hospital Center, Columbia University, New York, NY
Background: Investigations involving human cardiac tissue have rarely considered the anatomical site from which tissue or biopsy samples originate. It is often assumed that myocardial samples from a specific location represent the entire heart. However, animal studies suggest regional differences in gene and protein expression. Hypothesis: There are significant regional differences in gene expression in the human heart. Methods: We used two models to study this hypothesis. In the first, seven whole human hearts were obtained from patients who had donated hearts for scientific research. Table 1 shows the characteristics of the seven patients. The hearts were cut in 1 cm slices from apex to base. Samples from the apex, anterior wall, lateral wall, posterior wall, septum, and papillary muscle were obtained from both left and right ventricle. Tissue was also obtained from left and right atrium. Full thickness left ventricular tissue was further subdivided equally into inner, outer, and middle region. In the second model, hearts were removed from 300–350 g SpragueDawley rats and were divided into atria, right ventricle, left ventricle apex and base. Using quantitative RT-PCR, we measured transcript levels of MHC-beta, GLUT 1, and ANF in tissue samples from both models. Results: In human samples, there were significant differences in transcript levels between regions; however, only a few distinguishable patterns could be recognized among the seven hearts. ANF expression was highest in the inner one third of the myocardium. MHC beta and GLUT 1 transcript levels were increased in the right ventricle compared to left ventricle. In the atria, ANF transcript levels were highly expressed, while MHC beta and GLUT 1 expression was low. Furthermore, MHC beta expression was higher in right atria compared to left atria. Analogous to the human studies, MHC beta and GLUT 1 transcript levels were low in rat atria as compared to ventricles. On the other hand, MHC beta expression was higher in the left ventricle while GLUT 1 expression was not significantly different between ventricles. Conclusion: Despite the large variability in transcript levels among different regions in human hearts, certain patterns in gene expression emerged. These included differences between right and left ventricle, right and left atria, atria and ventricle, and between inner and outer regions of the myocardium. Different anatomical regions of the heart also differ in respect to gene expression. Patient characteristics Age Sex Race Cause of death Comorbid disease Gross pathology
35
35
66
M C Sepsis
M C Crush Injury
F C Brain Cancer
HTN, CRI Normal
Normal
Normal
71
65
87
16
F C MI
M C MI
M C Stroke
F C Suicide
HTN, obesity Hypertrophy
HTN, IDDM Dilated
HTN, hypothyroid Hypertophy
Normal
C ⫽ caucasian, HTN ⫽ hypertension, CRI ⫽ chronic renal insufficiency, IDDM ⫽ insulin dependent diabetes, MI ⫽ myocardial infarction
Background: In patients with heart failure (HF), left ventricular end-diastolic dimension (LVEDD) has been shown to be an important predictor of mortality. We have previously shown that in patients with nonischemic cardiomyopathy, the absence of inotropic contractile reserve (ICR) predicts mortality. In this present study, we sought to determine if there is a correlation between the degree of LVEDD and ICR. Methods: We evaluated 41 patients (mean age 57 ⫾ 9.4 ; 68 % males) with nonischemic cardiomyopathy (mean EF 31.9 ⫾ 10.2 , without significant coronary artery disease by coronary angiography within mean 36 ⫾ 88 days of dobutamine stress echocardiography). LVEF and wall motion analysis was performed by two experienced echocardiographers using a standard 16-segment model, and a 5-point scoring scale. Linear correlation analysis was used to determine the relationship between variables. Results: The mean LVEDD was 5.9 ⫾ 1.0 cm and mean segments with absence of ICR was 2.1 ⫾ 3.0. LVEDD index [LVEDD(cm) /Body Surface Area(m2)] was used to correct for body habitus. The mean LVEDD index was 3.05 ⫾ 0.5. The degree of LVEDD index had a significant correlation with absence of inotropic contractile reserve (Pearson r ⫽ 0.44755; p ⬍ 0.003). Conclusion: In patients with nonischemic cardiomyopathy, there is a significant correlation with the degree of left ventricular end diastolic dimension index and the absence of inotropic contractile reserve.
099
Regional Differences of Gene Expression in Human and Rodent Heart Saumya Sharma,1 Peter Razeghi,1 Ali Shakir,1 Brad Keneson,2 Fred Clubb,2 Heinrich Taegtmeyer1—1Cardiology, University of Texas Houston Medical School, Houston, TX; 2Pathology, Texas Heart Institute, Houston, TX
Left Ventricular End-Diastolic Dimension Correlates with Absence of Inotropic Contractile Reserve in Patients with Nonischemic Cardiomyopathy Ramzan M. Zakir,1 Marcin Kowalski,1 Reza Mohammadi,1 Siu-Sun Yao,1 Farooq A. Chaudhry1—1Cardiology, St.Luke’s-Roosevelt Hospital Center, Columbia University, New York, NY
Background: Investigations involving human cardiac tissue have rarely considered the anatomical site from which tissue or biopsy samples originate. It is often assumed that myocardial samples from a specific location represent the entire heart. However, animal studies suggest regional differences in gene and protein expression. Hypothesis: There are significant regional differences in gene expression in the human heart. Methods: We used two models to study this hypothesis. In the first, seven whole human hearts were obtained from patients who had donated hearts for scientific research. Table 1 shows the characteristics of the seven patients. The hearts were cut in 1 cm slices from apex to base. Samples from the apex, anterior wall, lateral wall, posterior wall, septum, and papillary muscle were obtained from both left and right ventricle. Tissue was also obtained from left and right atrium. Full thickness left ventricular tissue was further subdivided equally into inner, outer, and middle region. In the second model, hearts were removed from 300–350 g SpragueDawley rats and were divided into atria, right ventricle, left ventricle apex and base. Using quantitative RT-PCR, we measured transcript levels of MHC-beta, GLUT 1, and ANF in tissue samples from both models. Results: In human samples, there were significant differences in transcript levels between regions; however, only a few distinguishable patterns could be recognized among the seven hearts. ANF expression was highest in the inner one third of the myocardium. MHC beta and GLUT 1 transcript levels were increased in the right ventricle compared to left ventricle. In the atria, ANF transcript levels were highly expressed, while MHC beta and GLUT 1 expression was low. Furthermore, MHC beta expression was higher in right atria compared to left atria. Analogous to the human studies, MHC beta and GLUT 1 transcript levels were low in rat atria as compared to ventricles. On the other hand, MHC beta expression was higher in the left ventricle while GLUT 1 expression was not significantly different between ventricles. Conclusion: Despite the large variability in transcript levels among different regions in human hearts, certain patterns in gene expression emerged. These included differences between right and left ventricle, right and left atria, atria and ventricle, and between inner and outer regions of the myocardium. Different anatomical regions of the heart also differ in respect to gene expression. Patient characteristics Age Sex Race Cause of death Comorbid disease Gross pathology
35
35
66
M C Sepsis
M C Crush Injury
F C Brain Cancer
HTN, CRI Normal
Normal
Normal
71
65
87
16
F C MI
M C MI
M C Stroke
F C Suicide
HTN, obesity Hypertrophy
HTN, IDDM Dilated
HTN, hypothyroid Hypertophy
Normal
C ⫽ caucasian, HTN ⫽ hypertension, CRI ⫽ chronic renal insufficiency, IDDM ⫽ insulin dependent diabetes, MI ⫽ myocardial infarction
Background: In patients with heart failure (HF), left ventricular end-diastolic dimension (LVEDD) has been shown to be an important predictor of mortality. We have previously shown that in patients with nonischemic cardiomyopathy, the absence of inotropic contractile reserve (ICR) predicts mortality. In this present study, we sought to determine if there is a correlation between the degree of LVEDD and ICR. Methods: We evaluated 41 patients (mean age 57 ⫾ 9.4 ; 68 % males) with nonischemic cardiomyopathy (mean EF 31.9 ⫾ 10.2 , without significant coronary artery disease by coronary angiography within mean 36 ⫾ 88 days of dobutamine stress echocardiography). LVEF and wall motion analysis was performed by two experienced echocardiographers using a standard 16-segment model, and a 5-point scoring scale. Linear correlation analysis was used to determine the relationship between variables. Results: The mean LVEDD was 5.9 ⫾ 1.0 cm and mean segments with absence of ICR was 2.1 ⫾ 3.0. LVEDD index [LVEDD(cm) /Body Surface Area(m2)] was used to correct for body habitus. The mean LVEDD index was 3.05 ⫾ 0.5. The degree of LVEDD index had a significant correlation with absence of inotropic contractile reserve (Pearson r ⫽ 0.44755; p ⬍ 0.003). Conclusion: In patients with nonischemic cardiomyopathy, there is a significant correlation with the degree of left ventricular end diastolic dimension index and the absence of inotropic contractile reserve.