Abstract
Chronic pressure-overload and diabetes mellitus are two frequent disorders affecting the heart. We aimed to characterize myocardial structural and functional changes induced by both conditions. Pressure-overload was established in Wistar-han male rats by supra-renal aortic banding. Six-weeks later, diabetes was induced by streptozotocin (65 mg/kg,ip), resulting in four groups: SHAM, banding (BA), diabetic (DM) and diabetic-banding (DB). Six-weeks later, pressure-volume loops were obtained and left ventricular samples were collected to evaluate alterations in insulin signalling pathways, extracellular matrix as well as myofilament function and phosphorylation. Pressure-overload increased cardiomyocyte diameter (BA 22.0 ± 0.4 lm, SHAM 18.2 ± 0.3 lm) and myofilament maximal force (BA 25.7 ± 3.6 kN/m 2, SHAM 18.6 ± 1.4 kN/m 2), Ca 2+ sensitivity (BA 5.56 ± 0.02, SHAM 5.50 ± 0.02) as well as MyBP-C, Akt and Erk phosphorylation, while decreasing rate of force redevelopment (Ktr; BA 14.9 ± 1.1 s -1, SHAM 25.2 ± 1.5 s -1). At the extracellular matrix level, fibrosis (BA 10.8 ± 0.9%, SHAM 5.3 ± 0.6%), pro-MMP-2 and MMP-9 activities increased and, in vivo, relaxation was impaired (s; BA 14.0 ± 0.9 ms, SHAM 12.9 ± 0.4 ms). Diabetes increased cardiomyocyte diameter, fibrosis (DM 21.4 ± 0.4 lm, 13.9 ± 1.8%, DB 20.6 ± 0.4 lm, 13.8 ± 0.8%, respectively), myofilament Ca 2+sensitivity (DM 5.57 ± 0.02, DB 5.57 ± 0.01), advanced glycation end-product deposition (DM 4.9 ± 0.6 score/mm 2, DB 5.1 ± 0.4 score/mm2, SHAM 2.1 ± 0.3 score/mm 2), and apoptosis, while decreasing Ktr (DM 13.5 ± 1.9 s -1, DB 15.2 ± 1.4 s -1), Akt phosphorylation and MMP-9/TIMP-1 and MMP -1/ TIMP-1 ratios. Diabetic hearts were stiffer (higher enddiastolic-pressure: DM 7.0 ± 1.2 mmHg, DB 6.7 ± 0.7 mmHg, SHAM 5.3 ± 0.4 mmHg, steeper end-diastolicpressure- volume relation: DM 0.59 ± 0.18, DB 0.83 ± 0.17, SHAM 0.41 ± 0.10), and hypo-contractile (decreased end-systolic-pressure-volume-relation). DB animals presented further pulmonary congestion (Lungs/ body-weight: DB 5.23 ± 0.21 g/kg, SHAM 3.80 ± 0.14 g/kg) as this group combined overload-induced relaxation abnormalities and diabetes-induced stiffness. Diabetes mellitus and pressure overload led to distinct diastolic dysfunction phenotypes: while diabetes promoted myocardial stiffening, pressure overload impaired relaxation. The association of these damages accelerates the progression of diastolic heart failure progression in diabeticbanded animals.
| Original language | English |
|---|---|
| Pages (from-to) | 801-814 |
| Number of pages | 14 |
| Journal | Basic Research in Cardiology |
| Volume | 106 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Sep 2011 |
Fingerprint
Keywords
- Diabetes mellitus
- Diastolic function
- Hypertrophy
- Myocardial stiffness
- Pressure-overload
- Relaxation
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)
- Physiology
Cite this
Distinct mechanisms for diastolic dysfunction in diabetes mellitus and chronic pressure-overload. / Falcão-Pires, Inês; Palladini, Giuseppina; Goņalves, Nádia; Van Der Velden, Jolanda; Moreira-Goņalves, Daniel; Miranda-Silva, Daniela; Salinaro, Francesco; Paulus, Walter J.; Niessen, Hans W M; Perlini, Stefano; Leite-Moreira, Adelino F.
In: Basic Research in Cardiology, Vol. 106, No. 5, 09.2011, p. 801-814.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Distinct mechanisms for diastolic dysfunction in diabetes mellitus and chronic pressure-overload
AU - Falcão-Pires, Inês
AU - Palladini, Giuseppina
AU - Goņalves, Nádia
AU - Van Der Velden, Jolanda
AU - Moreira-Goņalves, Daniel
AU - Miranda-Silva, Daniela
AU - Salinaro, Francesco
AU - Paulus, Walter J.
AU - Niessen, Hans W M
AU - Perlini, Stefano
AU - Leite-Moreira, Adelino F.
PY - 2011/9
Y1 - 2011/9
N2 - Chronic pressure-overload and diabetes mellitus are two frequent disorders affecting the heart. We aimed to characterize myocardial structural and functional changes induced by both conditions. Pressure-overload was established in Wistar-han male rats by supra-renal aortic banding. Six-weeks later, diabetes was induced by streptozotocin (65 mg/kg,ip), resulting in four groups: SHAM, banding (BA), diabetic (DM) and diabetic-banding (DB). Six-weeks later, pressure-volume loops were obtained and left ventricular samples were collected to evaluate alterations in insulin signalling pathways, extracellular matrix as well as myofilament function and phosphorylation. Pressure-overload increased cardiomyocyte diameter (BA 22.0 ± 0.4 lm, SHAM 18.2 ± 0.3 lm) and myofilament maximal force (BA 25.7 ± 3.6 kN/m 2, SHAM 18.6 ± 1.4 kN/m 2), Ca 2+ sensitivity (BA 5.56 ± 0.02, SHAM 5.50 ± 0.02) as well as MyBP-C, Akt and Erk phosphorylation, while decreasing rate of force redevelopment (Ktr; BA 14.9 ± 1.1 s -1, SHAM 25.2 ± 1.5 s -1). At the extracellular matrix level, fibrosis (BA 10.8 ± 0.9%, SHAM 5.3 ± 0.6%), pro-MMP-2 and MMP-9 activities increased and, in vivo, relaxation was impaired (s; BA 14.0 ± 0.9 ms, SHAM 12.9 ± 0.4 ms). Diabetes increased cardiomyocyte diameter, fibrosis (DM 21.4 ± 0.4 lm, 13.9 ± 1.8%, DB 20.6 ± 0.4 lm, 13.8 ± 0.8%, respectively), myofilament Ca 2+sensitivity (DM 5.57 ± 0.02, DB 5.57 ± 0.01), advanced glycation end-product deposition (DM 4.9 ± 0.6 score/mm 2, DB 5.1 ± 0.4 score/mm2, SHAM 2.1 ± 0.3 score/mm 2), and apoptosis, while decreasing Ktr (DM 13.5 ± 1.9 s -1, DB 15.2 ± 1.4 s -1), Akt phosphorylation and MMP-9/TIMP-1 and MMP -1/ TIMP-1 ratios. Diabetic hearts were stiffer (higher enddiastolic-pressure: DM 7.0 ± 1.2 mmHg, DB 6.7 ± 0.7 mmHg, SHAM 5.3 ± 0.4 mmHg, steeper end-diastolicpressure- volume relation: DM 0.59 ± 0.18, DB 0.83 ± 0.17, SHAM 0.41 ± 0.10), and hypo-contractile (decreased end-systolic-pressure-volume-relation). DB animals presented further pulmonary congestion (Lungs/ body-weight: DB 5.23 ± 0.21 g/kg, SHAM 3.80 ± 0.14 g/kg) as this group combined overload-induced relaxation abnormalities and diabetes-induced stiffness. Diabetes mellitus and pressure overload led to distinct diastolic dysfunction phenotypes: while diabetes promoted myocardial stiffening, pressure overload impaired relaxation. The association of these damages accelerates the progression of diastolic heart failure progression in diabeticbanded animals.
AB - Chronic pressure-overload and diabetes mellitus are two frequent disorders affecting the heart. We aimed to characterize myocardial structural and functional changes induced by both conditions. Pressure-overload was established in Wistar-han male rats by supra-renal aortic banding. Six-weeks later, diabetes was induced by streptozotocin (65 mg/kg,ip), resulting in four groups: SHAM, banding (BA), diabetic (DM) and diabetic-banding (DB). Six-weeks later, pressure-volume loops were obtained and left ventricular samples were collected to evaluate alterations in insulin signalling pathways, extracellular matrix as well as myofilament function and phosphorylation. Pressure-overload increased cardiomyocyte diameter (BA 22.0 ± 0.4 lm, SHAM 18.2 ± 0.3 lm) and myofilament maximal force (BA 25.7 ± 3.6 kN/m 2, SHAM 18.6 ± 1.4 kN/m 2), Ca 2+ sensitivity (BA 5.56 ± 0.02, SHAM 5.50 ± 0.02) as well as MyBP-C, Akt and Erk phosphorylation, while decreasing rate of force redevelopment (Ktr; BA 14.9 ± 1.1 s -1, SHAM 25.2 ± 1.5 s -1). At the extracellular matrix level, fibrosis (BA 10.8 ± 0.9%, SHAM 5.3 ± 0.6%), pro-MMP-2 and MMP-9 activities increased and, in vivo, relaxation was impaired (s; BA 14.0 ± 0.9 ms, SHAM 12.9 ± 0.4 ms). Diabetes increased cardiomyocyte diameter, fibrosis (DM 21.4 ± 0.4 lm, 13.9 ± 1.8%, DB 20.6 ± 0.4 lm, 13.8 ± 0.8%, respectively), myofilament Ca 2+sensitivity (DM 5.57 ± 0.02, DB 5.57 ± 0.01), advanced glycation end-product deposition (DM 4.9 ± 0.6 score/mm 2, DB 5.1 ± 0.4 score/mm2, SHAM 2.1 ± 0.3 score/mm 2), and apoptosis, while decreasing Ktr (DM 13.5 ± 1.9 s -1, DB 15.2 ± 1.4 s -1), Akt phosphorylation and MMP-9/TIMP-1 and MMP -1/ TIMP-1 ratios. Diabetic hearts were stiffer (higher enddiastolic-pressure: DM 7.0 ± 1.2 mmHg, DB 6.7 ± 0.7 mmHg, SHAM 5.3 ± 0.4 mmHg, steeper end-diastolicpressure- volume relation: DM 0.59 ± 0.18, DB 0.83 ± 0.17, SHAM 0.41 ± 0.10), and hypo-contractile (decreased end-systolic-pressure-volume-relation). DB animals presented further pulmonary congestion (Lungs/ body-weight: DB 5.23 ± 0.21 g/kg, SHAM 3.80 ± 0.14 g/kg) as this group combined overload-induced relaxation abnormalities and diabetes-induced stiffness. Diabetes mellitus and pressure overload led to distinct diastolic dysfunction phenotypes: while diabetes promoted myocardial stiffening, pressure overload impaired relaxation. The association of these damages accelerates the progression of diastolic heart failure progression in diabeticbanded animals.
KW - Diabetes mellitus
KW - Diastolic function
KW - Hypertrophy
KW - Myocardial stiffness
KW - Pressure-overload
KW - Relaxation
UR - http://www.scopus.com/inward/record.url?scp=80054698973&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80054698973&partnerID=8YFLogxK
U2 - 10.1007/s00395-011-0184-x
DO - 10.1007/s00395-011-0184-x
M3 - Article
C2 - 21533831
AN - SCOPUS:80054698973
VL - 106
SP - 801
EP - 814
JO - Basic Research in Cardiology
JF - Basic Research in Cardiology
SN - 0300-8428
IS - 5
ER -