Particulate matter exposure exacerbates high glucose-induced cardiomyocyte dysfunction through ROS generation

Area of Science:

• Cardiovascular Disease Research
• Diabetology
• Environmental Health Science

Background:

• Diabetes mellitus and fine particulate matter from diesel exhaust (DEP) are significant contributors to cardiovascular disease (CVD).
• Diabetic cardiomyopathy, a complication of diabetes, is associated with high CVD mortality.
• Inhaled fine DEP (<2.5 µm) can enter circulation, but mechanisms affecting diabetic cardiomyocytes are unclear.

Purpose of the Study:

• To investigate the impact of DEP exposure on cardiomyocyte function and reactive oxygen species (ROS) generation in high glucose (HG)-exposed diabetic rat ventricular myocytes.
• To test the hypothesis that DEP exacerbates contractile dysfunction through ROS generation in HG-exposed cardiomyocytes.

Main Methods:

• Isolated rat ventricular myocytes were cultured and exposed to fine DEP (0.1 µg/ml) and/or high glucose (HG, 25.5 mM).
• Sarcomeric contractile properties (peak shortening, time to shortening/relengthening, velocities) were measured using an IonOptix system.
• Intracellular ROS generation was quantified using hydroethidine/ethidium confocal microscopy.

Main Results:

• DEP exposure significantly increased time to 90% relengthening (TR(90)), decreased peak shortening (PS) and maximal shortening/relengthening velocities (±dL/dt) in HG-exposed myocytes.
• DEP and HG co-exposure enhanced intracellular ROS generation compared to controls.
• Antioxidants (Tiron, N-Acetyl-L-cysteine) fully restored contractile function in all treatment groups.
• ROS generation was linked to mitochondrial inhibition in HG-treated cells and NADPH oxidase inhibition in DEP-treated cells.

Conclusions:

• Diesel exhaust particles exacerbate myocardial dysfunction in cardiomyocytes exposed to high glucose conditions.
• This exacerbation appears to be mediated by various reactive oxygen species (ROS) generation pathways.
• Targeting ROS pathways may offer therapeutic strategies for diabetic cardiomyopathy exacerbated by air pollution.