1. No conflict of interest
Effects of exercise on the cardiovascular system
Cardiovascular Rehabilitation Training Course
22-23 March 2018, Lviv/Ukraine
Dominique Hansen, FESC
No conflict of interest

2. Learning objectives
To obtain an understanding of the molecular impact of exercise on the vascular system
To obtain an understanding of the molecular impact of exercise on the cardiomyocyte
To understand the current limitations in this field of research
To know what remains to be studied

3. ?

4. Sources

5. FBF: forearm blood flow

8. eNOS (endothelial NO synthase) activation is key to NO activation

9. Ca+-dependent vasodilation
Step 1a: Ca+ inflow interacts with calmodulin, leading to eNOS release

10. Ca+-dependent vasodilation
Step 1b: eNOS is attached to caveolin

11. Ca+-dependent vasodilation
Step 2: eNOS associates with HSP-90 to prevent degradation

12. Ca+-dependent vasodilation
Step 2: dimerization of the enzyme, leading to eNOS activation/NO production

13. VEGFR2 and PECAM1-dependent vasodilation (both mechanical receptors)
Step 1: activation of cascade of different enzymes

14. VEGFR2 and PECAM1-dependent vasodilation (both mechanical receptors)
Step 2: eNOS phosphorylation followed by NO production

18. Effects of Exercise Training on Left Ventricular Function and Peripheral Resistance in Patients With Chronic Heart Failure
Hambrecht R, et al. JAMA 2000; 283:

19. Lowered blood pressure
Improved vasodilation ?

20. Hyperactive Ubiquitin Proteasome System (UPS)

21. Exercise lowers UPS activity
WR: Wistar Rat, EX: Exercise, SHR: spontaneous hypertensive

22. Impaired Ca+ handling
Leads to disturbed excitation-contraction coupling
Circulation Research. 2013;113:

23. Improved Ca+ handling by exercise training

24. Cardiac remodelling

25. Improved cardiac remodelling by exercise training

26. Improved cardiac remodelling by exercise training

27. Enhanced angiogenesis

28. Autonomic function Ageing is associated with
Β-adrenergic receptor desensitisation
Probably due to long-term increased circulatory norepineprine concentrations
Resulting into impaired Ca+ handling
Leading to impaired inotropic and chronotropic responses

29. Myocardial fibrosis

30. Exercise training lowers fibrosis

31. Worse mitochondrial function by aging

32. Improved mitochondrial function by exercise

33. Improved mitochondrial function by exercise

34. What remains to be studied?
Specific molecular cascades
Exercise training modalities
Strength training
Exercise intensity
Exercise volume
Translation to humans
Stress during exercise
Genetic modification
Male vs. female animals
Interaction with drugs and diet

35. Conclusions
Exercise training is capable to positively affect molecular mechanisms involved in:
Vascular endothelial function
Cardiomyocyte function
These data should be interpreted in light of the study limitations