Cardiac oxidative stress is an early event associated with
diabetic cardiomyopathy, triggered by
hyperglycemia. We tested the hypothesis that targeting left-ventricular (LV)
reactive oxygen species (ROS) upregulation subsequent to
hyperglycemia attenuates
type 1 diabetes-induced LV remodeling and dysfunction, accompanied by attenuated proinflammatory markers and cardiomyocyte apoptosis. Male 6-week-old mice received either
streptozotocin (55mg/kg/day for 5 days), to induce
type 1 diabetes, or
citrate buffer vehicle. After 4 weeks of
hyperglycemia, the mice were allocated to
coenzyme Q10 supplementation (10mg/kg/day), treatment with the
angiotensin-converting-enzyme inhibitor (ACE-I)
ramipril (3mg/kg/day), treatment with
olive oil vehicle, or no treatment for 8 weeks.
Type 1 diabetes upregulated LV
NADPH oxidase (Nox2, p22(
phox), p47(
phox) and
superoxide production), LV
uncoupling protein UCP3 expression, and both LV and systemic oxidative stress (LV 3-
nitrotyrosine and plasma lipid peroxidation). All of these were significantly attenuated by
coenzyme Q10.
Coenzyme Q10 substantially limited
type 1 diabetes-induced impairments in LV diastolic function (E:A ratio and deceleration time by echocardiography, LV end-diastolic pressure, and LV -dP/dt by micromanometry), LV remodeling (cardiomyocyte
hypertrophy, cardiac fibrosis, apoptosis), and LV expression of proinflammatory mediators (
tumor necrosis factor-α, with a similar trend for
interleukin IL-1β).
Coenzyme Q10's actions were independent of
glycemic control, body mass, and blood pressure.
Coenzyme Q10 compared favorably to improvements observed with
ramipril. In summary, these data suggest that
coenzyme Q10 effectively targets LV ROS upregulation to limit type 1
diabetic cardiomyopathy.
Coenzyme Q10 supplementation may thus represent an effective alternative to ACE-Is for the treatment of cardiac complications in type 1 diabetic patients.