Left ventricle function and post-transcriptional events with exercise training in pigs.

Area of Science:

• Cardiovascular Physiology
• Molecular Biology
• Exercise Science

Background:

• Standardized exercise improves cardiovascular fitness, but its impact on left ventricular (LV) diastolic function and underlying microRNA (miR) regulation remains unclear.
• Investigating the relationship between exercise-induced LV remodeling and specific miRs is crucial for understanding myocardial mechanics.

Purpose of the Study:

• To test if adaptive LV remodeling from exercise training is associated with specific miRs regulating LV myocardial stiffness and geometry.
• To explore the molecular pathways, including miRs, influenced by a large animal exercise protocol.

Main Methods:

• A 4-week exercise training protocol was implemented in pigs (n=9), with non-exercised pigs (n=6) as controls.
• Left ventricular (LV) chamber stiffness (KC) and regional myocardial stiffness (rKm) were measured using Doppler/speckle tracking echocardiography.
• An 84 miR array was used to identify changes in miRs, with correlations to stiffness and inflammatory markers (NLRP-3 mRNA).

Main Results:

• Exercise training significantly reduced LV chamber stiffness (KC) by ~50% and regional myocardial stiffness (rKm) by ~30% (p < 0.05).
• 34 out of 84 miRs changed with exercise; 8 miRs correlated with reduced KC and mapped to matrix and calcium handling pathways.
• Specific miRs (miR-22, miR-30e) decreased with exercise, correlating with reduced inflammasome (NLRP-3) activity and mRNA levels (p < 0.05).

Conclusions:

• Chronic exercise effectively reduces LV chamber and myocardial stiffness in a large animal model.
• Exercise-induced reductions in stiffness are correlated with specific miRs involved in myocardial relaxation and inflammatory pathways.
• Myocardial miR profiling can elucidate the mechanisms behind exercise-induced changes in LV structure and function.