Abstract
Insulin resistance (IR) and systemic hypertension are independently associated with heart failure. We reported previously that nitric oxide synthase 3 (NOS3) has a beneficial effect on left ventricular (LV) remodeling and function after pressure-overload in mice. The aim of our study was to investigate the interaction of IR and NOS3 in pressure-overload-induced LV remodeling and dysfunction. Wild-type (WT) and NOS3-deficient (NOS3~ /~) mice were fed either a standard diet (SD) or a high-fat diet (HFD) to induce IR. After 9 days of diet, mice underwent transverse aortic constriction (TAC). LV structure and function were assessed serially using echocardiography. Cardiomyocytes were isolated, and levels of oxidative stress were evaluated using 2',7'-dichlorodihydrofluorescein diacetate. Cardiac mitochondria were isolated, and mitochondrial respiration and ATP production were measured. TAC induced LV remodeling and dysfunction in all mice. The TAC-induced decrease in LV function was greater in SD-fed NOS3~ /~ mice than in SD-fed WT mice. In contrast, HFD-fed NOS3~ /~ developed less LV remodeling and dysfunction and had better survival than did HFD-fed WT mice. Seven days after TAC, oxidative stress levels were lower in cardiomyocytes from HFD-fed NOS3~ /~ than in those from HFD-fed WT. N^-nitro-L-arginine methyl ester and mitochondrial inhibitors (rotenone and 2-thenoyltri-fluoroacetone) decreased oxidative stress levels in cardiomyocytes from HFD-fed WT mice. Mitochondrial respiration was altered in NOS3~ /~ mice but did not worsen after HFD and TAC. In contrast with its protective role in SD, NOS3 increases LV adverse remodeling after pressure overload in HFD-fed, insulin resistant mice. Interactions between NOS3 and mitochondria may be responsible for increased oxidative stress levels in HFD-fed WT mice hearts.
| Original language | English |
|---|---|
| Journal | American Journal of Physiology - Heart and Circulatory Physiology |
| Volume | 301 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Nov 2011 |
| Externally published | Yes |
Fingerprint
Keywords
- Cardiac dysfunction
- Oxidative stress
ASJC Scopus subject areas
- Physiology
- Physiology (medical)
- Cardiology and Cardiovascular Medicine
Cite this
Nitric oxide synthase 3 deficiency limits adverse ventricular remodeling after pressure overload in insulin resistance. / Kurtz, Baptiste; Thibault, Helene B.; Raher, Michael J.; Popovich, John R.; Cawley, Sharon; Atochin, Dmitriy N.; Hayton, Sarah; Shakartzi, Hannah R.; Huang, Paul L.; Bloch, Kenneth D.; Buys, Emmanuel; Scherrer-Crosbie, Marielle.
In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 301, No. 5, 11.2011.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Nitric oxide synthase 3 deficiency limits adverse ventricular remodeling after pressure overload in insulin resistance
AU - Kurtz, Baptiste
AU - Thibault, Helene B.
AU - Raher, Michael J.
AU - Popovich, John R.
AU - Cawley, Sharon
AU - Atochin, Dmitriy N.
AU - Hayton, Sarah
AU - Shakartzi, Hannah R.
AU - Huang, Paul L.
AU - Bloch, Kenneth D.
AU - Buys, Emmanuel
AU - Scherrer-Crosbie, Marielle
PY - 2011/11
Y1 - 2011/11
N2 - Insulin resistance (IR) and systemic hypertension are independently associated with heart failure. We reported previously that nitric oxide synthase 3 (NOS3) has a beneficial effect on left ventricular (LV) remodeling and function after pressure-overload in mice. The aim of our study was to investigate the interaction of IR and NOS3 in pressure-overload-induced LV remodeling and dysfunction. Wild-type (WT) and NOS3-deficient (NOS3~ /~) mice were fed either a standard diet (SD) or a high-fat diet (HFD) to induce IR. After 9 days of diet, mice underwent transverse aortic constriction (TAC). LV structure and function were assessed serially using echocardiography. Cardiomyocytes were isolated, and levels of oxidative stress were evaluated using 2',7'-dichlorodihydrofluorescein diacetate. Cardiac mitochondria were isolated, and mitochondrial respiration and ATP production were measured. TAC induced LV remodeling and dysfunction in all mice. The TAC-induced decrease in LV function was greater in SD-fed NOS3~ /~ mice than in SD-fed WT mice. In contrast, HFD-fed NOS3~ /~ developed less LV remodeling and dysfunction and had better survival than did HFD-fed WT mice. Seven days after TAC, oxidative stress levels were lower in cardiomyocytes from HFD-fed NOS3~ /~ than in those from HFD-fed WT. N^-nitro-L-arginine methyl ester and mitochondrial inhibitors (rotenone and 2-thenoyltri-fluoroacetone) decreased oxidative stress levels in cardiomyocytes from HFD-fed WT mice. Mitochondrial respiration was altered in NOS3~ /~ mice but did not worsen after HFD and TAC. In contrast with its protective role in SD, NOS3 increases LV adverse remodeling after pressure overload in HFD-fed, insulin resistant mice. Interactions between NOS3 and mitochondria may be responsible for increased oxidative stress levels in HFD-fed WT mice hearts.
AB - Insulin resistance (IR) and systemic hypertension are independently associated with heart failure. We reported previously that nitric oxide synthase 3 (NOS3) has a beneficial effect on left ventricular (LV) remodeling and function after pressure-overload in mice. The aim of our study was to investigate the interaction of IR and NOS3 in pressure-overload-induced LV remodeling and dysfunction. Wild-type (WT) and NOS3-deficient (NOS3~ /~) mice were fed either a standard diet (SD) or a high-fat diet (HFD) to induce IR. After 9 days of diet, mice underwent transverse aortic constriction (TAC). LV structure and function were assessed serially using echocardiography. Cardiomyocytes were isolated, and levels of oxidative stress were evaluated using 2',7'-dichlorodihydrofluorescein diacetate. Cardiac mitochondria were isolated, and mitochondrial respiration and ATP production were measured. TAC induced LV remodeling and dysfunction in all mice. The TAC-induced decrease in LV function was greater in SD-fed NOS3~ /~ mice than in SD-fed WT mice. In contrast, HFD-fed NOS3~ /~ developed less LV remodeling and dysfunction and had better survival than did HFD-fed WT mice. Seven days after TAC, oxidative stress levels were lower in cardiomyocytes from HFD-fed NOS3~ /~ than in those from HFD-fed WT. N^-nitro-L-arginine methyl ester and mitochondrial inhibitors (rotenone and 2-thenoyltri-fluoroacetone) decreased oxidative stress levels in cardiomyocytes from HFD-fed WT mice. Mitochondrial respiration was altered in NOS3~ /~ mice but did not worsen after HFD and TAC. In contrast with its protective role in SD, NOS3 increases LV adverse remodeling after pressure overload in HFD-fed, insulin resistant mice. Interactions between NOS3 and mitochondria may be responsible for increased oxidative stress levels in HFD-fed WT mice hearts.
KW - Cardiac dysfunction
KW - Oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=80355134446&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80355134446&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.00744.2010
DO - 10.1152/ajpheart.00744.2010
M3 - Article
VL - 301
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
SN - 0363-6135
IS - 5
ER -