RICERCA ITALIANA     

Molecular and cellular mechanisms underlying exercise-induced protection

Università degli Studi di Milano

Abstract

1. This project originates from the observation that chronic moderate aerobic exercise (training) reduces the incidence of the major cardiovascular and degenerative diseases. Although training has became an integrative part of preventive and rehabilitative medicine in the most advanced countries, there is still considerable space for targeted basic studies:
1.1 The molecular mechanisms underlying training-induced protection are not yet well understood. For example, for what concerns myocardial protection, it is unclear which factor(s) play(s) the most important roles among preconditioning (i.e., the development of transitory resistance to severe insults as a result of prior exposure to moderate insults), development of collateral coronary arteries, induction of heat shock proteins, improved anti-oxidant capacity and blood coagulation control.
1.2 It is unclear whether training-induced protection is attributable to training per se or to the associated lifestyle changes. For example, abstinence from smoking, moderate food and beverage intake and decreased psychological stress are variables that, although concurring in eliciting protection, tend to confound the cause-effect mechanisms.
1.3 The mechanisms underlying loss of protection after training cessation (detraining) are poorly elucidated. This issue is relevant not only for practical purposes, but it is also useful in order to understand to a larger extent the molecular mechanisms mediating >>>

Principal Investigator

Arsenio VEICSTEINAS Università degli Studi di MILANO

Research Objectives

1. Analysis of the problem. The epidemiological findings, as well as the basic hypotheses raised from studies in human, animal and in vitro models, are reviewed in the "Background" section. These findings support the idea that moderate, regular aerobic physical exercise (training) reduces the weight of a number of risk factors for cardiovascular (coronary heart disease, ictus, hypertension) and degenerative (atherosclerosis, type II diabetes) diseases. Training, therefore, should trigger protective mechanisms for several tissues, especially the myocardium. Despite the considerable epidemiological evidence, however, the molecular mechanisms underlying this phenomenon have not yet been fully clarified.

2. Aim of the project. To emphasise the role of training in eliciting cytoprotection, all the potential confounding variables not related to training must be either eliminated or minimised. To this aim, we propose an animal model where male rats from a homogeneous population are subjected to training of intensity and duration comparable to that of humans who take physical regular exercise. At the end of the training and detraining periods, the rats will be sacrificed and various tissues will be harvested for a number of biochemical, molecular, morphologic and physiologic analyses.

3. Primary objectives:
3.1 To confirm that training is protective in terms of myocardial resistance to ischemia-reperfusion injury independently of the associated >>>

First Results

The end of this Phase will match two primary objectives of this project:
- Confirming the hypothesis that aerobic training is protective irrespectively of life style.

- Investigating the expression of key proteins and genes that potentially mediate the training-induced response, change the antioxidant response and alter muscle morphology.Results expected from Phase 2
The end of Phase 3 will match the last of the primary objectives:
- Determining to what extent the protective effects of training persist after training cessation for one month.
At the end of this Phase we will also evaluate possible further development of this project. Though rooted to knowledge already acquired by the involved Units, the present project is innovative in many aspects and is likely to open new lines of study. For example, if exercise results to be protective, further studies will be needed to determine the relationships between training intensity or frequency and the extent of protection. Other questions may concern the effects on the exercise-induced protection of dietary components, such as antioxidants or caloric uptake, age, gender and common disease risk factors (e.g., hyperglycemia, hypertriglyceridemia, hypercholesterolemia). The present project makes an effort to accelerate the transfer to human applications and may constitute the starting point for the identification of specific markers that will enable to develop kits or microarrays for the >>>

Timescale

24 months

National and international background

1 Epidemiology of moderate physical exercise. Notwithstanding increasing evidence that moderate physical exercise prevents the development and progression of chronic degenerative diseases such as atherosclerosis, coronary heart disease and type II diabetes mellitus (Haennel and Lemire, 2002; Marliss and Vranic, 2002), most people in industrialised countries customarily lead sedentary lives. The beneficial effect of moderate regular exercise on the main risk factors for cardiovascular disease was documented by a number of epidemiological studies, including the Multiple Risk Factor Intervention Trial (Leon et al., 1987), the Harvard Alumni Study (Paffenbarger et al., 1993), the Lipid Research Clinic Mortality Follow-up Study (Ekelund et al., 1988) and several large scale prospective studies (Blair et al., 1989). These studies clearly indicate that physically active people have lower incidence of myocardial infarction and greater survival from heart attack compared with sedentary counterparts (Berlin and Colditz, 1990). Exercise programs in sedentary people must be carefully tailored, and the recommendations contained in the 2001 revision of the 1995 guidelines proposed by the American College of Cardiology and the American Heart Association (Fletcher et al., 2001) suggest that a three times a week volume of exercise of 1400 Kcal/week is necessary and sufficient to produce the expected benefits (American College of Sports Medicine, Resource Manual for guidelines for exercise >>>