Monday, March 2, 2015

Effects of exercise training on the heart 

One of the most amazing organs in both humans and animals is the heart. I mean, it has to be right? For Heaven’s sakes, there is a day in February dedicated to this particular organ! Can you guess what is it? That’s right you lovebirds, it’s called Valentine’s Day!



But honestly, who cares, especially since it’s already March! Let’s get to some cool science about the heart! The heart is a muscular organ that pumps blood and provides oxygen (O2) and nutrients throughout the entire body. Even more so, it also assists with waste removal. Within humans and many other mammals, the heart is divided into 4 separate chambers: the left and right atria, and the left and right ventricles. Furthermore, the heart pumps 2 types of blood: deoxygenated blood and oxygenated blood. Oxygenated blood contains hemoglobin, an iron-containing protein that facilitates oxygen transport throughout the body. Deoxygenated blood on the other hand, also contains hemoglobin, but doesn’t have oxygen bound to it.

Anatomical diagram of the heart. Note the 4 chambers (right and left atrium, right and left ventricles).


Hemoglobin can bind up to 4 oxygen molecules. Oxygen is picked up from the pulmonary alveolus and delivered to cells.
           
When looking at the heart, there are 2 types of circulations: pulmonary and systemic circulation. In pulmonary circulation, oxygen is collected from the lungs through inhalation and releases carbon dioxide (CO2) through exhalation. For systemic circulation however, oxygenated blood is transported through other parts of the body such as the arms and legs. Once the oxygen is spent, deoxygenated blood flows back through the pulmonary circuit for more oxygen before being distributed again throughout the body. Also note that blood flows in only one direction, starting from the atria and to the ventricles. For example, let’s take a look at the right side of the heart (also called anatomical left). The right side of the heart is responsible for collecting deoxygenated blood from the body via the superior and inferior vena cava. Deoxygenated blood flows into the right atrium, towards the right ventricle. Throughout the heart, there are these structures called valves. These valves shut tight after blood flows through to prevent backflow. For instance, after blood enters the right ventricle, the tricuspid valve closes to prevent blood from flowing back into the right atrium. Once deoxygenated blood reaches the right ventricle, it flows to the pulmonary artery (pulmonary circulation) where CO2 can be exchanged for O2. This oxygenated blood, now flows to the left side of the heart, where it enters the left atrium via the pulmonary vein. It then flows into the left ventricle (mitral valve closes) and eventually to the aorta (aortic valve closes). Once it reaches the aorta, the oxygenated blood is distributed throughout the entire body. When it reaches the capillaries, oxygen and nutrients will be exchanged for waste products and CO2 from cells and tissues. 


Diagram of the heart illustrating systemic and pulmonary circulation. In pulmonary circulation, CO2 gets exchanged for O2 in the lungs. This now oxygenated blood goes through systemic circulation, where it gets delivered to organs and tissues of the body.

So that’s cool right? We know how the heart works now. But honestly, I didn’t just want to just give you guys a small talk on how the heart works. As a fanatic distance runner, I was always interested in how exercise affects the heart. More specifically in scientific terms, I’m more interested in how exercise training can affect the cardiovascular system, especially at the molecular level. Thus, without further ado, let’s dive into it than!

We all know that physical activity is good for us. In fact, the American Heart Association recommends at least 30 minutes a day of moderate-intensity aerobic activity at least 5 days a week (AHA). The question then becomes HOW is it good for us? We all know WHY it’s good for us. We hear it all the time: exercise reduces the risk of heart disease, boosts morality, and etc. But what’s happening within the heart that actually exerts these positive effects? Let’s first talk about in general what happens to the heart when you exercise, and then we’ll go more into the molecular mechanisms responsible for these outcomes. But first, check out this really cool video of the beating heart:

3D echocardiogram of a beating heart. Notice the opening and closing of the mitral valve to prevent backflow.


One of the main things that happen is a change in the left ventricular mass and function. In a previous study from Ferhonen et al. 2001, there was a significant decrease in left ventricular mass and function in sedentary individuals (Perhonen et al. 2001) compared to highly active individuals. On the other hand, when healthy sedentary individuals followed a 12-week exercise training program, the cardiac cells or cardiomyocytes (cells within the heart), underwent hypertrophy and grew larger (Sipola et al. 2009). These 2 studies showed that the heart morphology is susceptible to plasticity. In other words, the heart can change its size, shape, and even mass. That’s crazy right?! 
                       

What about individuals who regularly undergo high-intensity exercise 5-6 days a week? These individuals have what is known as the “athlete’s heart”. The athlete’s heart is much larger compared to inactive individuals. In addition, studies have found that the types of exercises you do can definitely impact what “type” of athlete’s heart you may have. For instance, in a large cohort study containing 1,451 athletes, Pluim et al. (2000) found that endurance athletes (runners, swimmers, cyclists, etc.) are more susceptible to myocardial hypertrophy than strength athletes (weightlifters, wrestlers, sprinters, etc.). In addition, endurance-trained athletes had a LV end-diastolic diameter of 53.7mm compared with 49.6mm within non-endurance trained athletes (Pluim et al. 2000). What is the physiological mechanism behind the increase in left ventricular hypertrophy? Neri et al. (2001) found that this process is mediated by a specific protein called insulin-like growth factor (IGF-1) and phophoinositide-3 kinase (PI3K). Furthermore, studies in mice found that transgenic mice with decreased expression levels of PI3K had reduced cardiac size and did not undergo as much exercise-induced cardiac hypertrophy compared to mice with normal PI3K levels (Neri et al. 2001).

An athlete’s heart (25x18cm) vs a non-athlete’s heart (15x12cm).  

Positive correlation between cardiac IGF-1 and left ventricular mass index (LVMI). In other words, athletes have bigger heart because their cardiac cells express higher levels of IGF-1.

Moreover, it has been found that small RNA molecules, called microRNAs (miRNAs or miRs), also play a role in cardiac hypertrophy (Carè et al. 2007). miRNAs are small RNA molecules composed of about 22 nucleotides. They are found in animals and plants that are responsible for targeting mRNA for cleavage and translational repression (Bartel, 2004). In other words, these molecules prevent protein expression and therefore inhibit specific protein functions. Carè et al. found that there are decreased miR-133 and miR-1 expression levels within cardiac hypertrophy models within both mice and humans. Furthermore, the researchers also discovered that in vivo (meaning within normal biological environments) injection of an antagomir (inhibitors of miRs, such as miR-133 or miR-1) promoted cardiac hypertrophy.

Note how much bigger the heart is within the antagomir injected group (black bars) versus the control group (white bars) with injected saline. In addition, after injection with antagomir, there was a significant increase in interventricular septum thickness (IVSd), left ventricular posterior wall thickness (LVPWd), left ventricular mass (LVM), and ratio of left ventricle weight to body weight (LVW/BW) compared to the control.

Ok. So we now know what happens to our hearts after we exercise. What about when we stop exercising for a few days or a few weeks? In a study done by Kemi et al. (2004), the authors assessed cardiomyocyte dimensions, contractile capacity, and maximal oxygen uptake (VO2 max) at 2, 4, 8, and 13 weeks of training followed by 2 and 4 weeks of detraining. When the mice were exposed to a high-intensity treadmill running, regime, the mice had a higher VO2 max, ventricular weights and dimensions, and more efficient contractility; 2 weeks of detraining however, decreased all of these parameters (Kemi et al. 2004). In other words, you better use it or you’ll lose it! 

Exercise training increases VO2 max but decreases again if training stops. Note that sedentary individuals (SED10, 2, and 4) have a lower VO2 compared to trained individuals (TR10) and even detrained individuals (DETR2, 4).

You don’t want to lose it, so use it!


So what’s the take home message here folks? I’m pretty sure everyone here knows it: go out and be physically active. It doesn’t take much to maintain a healthy lifestyle. Just take 15-30 minutes a day for 5 days of the week out of your chaotic schedule to make it happen. As my music professor during my undergraduate at SJSU always told me, a little everyday goes a long way. Consistency is the most important thing. If you’re consistent, you’ll definitely get that so-called athletes heart. For the gentlemen in the house, the ladies will love it. For the ladies, the guys will definitely love it! So…once you’re done reading this blog, go to the gym, shoot some hoops at the basketball courts, or whatever. Just do your thing. Better yet, at least take a walk or run around the block…literally…


When you do decide to exercise though, just keep this in mind for motivation: 


Thanks for reading! - Kevin Minh Tran

References in order of citation


Perhonen MA, F. Franco, L.D. Lane, J.C. Buckey, C.G. Blomqvist, J.E. Zerwekh, R.M. Peshock, P.T. Weatherall, and B.D. Levine. 2001. Cardiac atrophy after bed rest and spaceflight. Journal of Applied Physioly 91:645–653.

Sipola P, J. Heikkinen, D.E. Laaksonen, and R. Kettunen. 2009. Influence of 12 weeks of jogging on magnetic resonance-determined left ventricular characteristics in previously sedentary subjects free of cardiovascular disease. American Journal of Cardiology 103:567–571.

Pluim BM, A.H. Zwinderman, A. van der Laarse, and E.E. van der Wall. 2000. The athlete’s heart: a meta-analysis of cardiac structure and function. Circulation 101:336–344.

Neri Serneri G.G., M. Boddi, P.A. Modesti, I. Cecioni, M. Coppo, L. Padeletti, A. Michelucci, A. Colella, and G. Galanti. 2001. Increased cardiac sympathetic activity and insulin-like growth factor-I formation are associated with physiological hypertrophy in athletes. Circulation Research 89:977–982.

Carè A., D. Catalucci, F. Felicetti, D. Bonci, A. Addario, P. Gallo, M.L. Bang, P. Segnalini, Y. Gu, N.D. Dalton, L. Elia, M.V.G. Latronico, M. Hoydal, C. Autore, M.A. Russo, G.W. Dorn, O. Ellingsen, P. Ruiz-Lozano, K.L Peterson, C.M. Croce, C. Peschle, and G. Condorelli. 2007. MicroRNA-133 controls cardiac hypertrophy. Nature Medicine 13: 613–618.

Bartel, D. P. 2004. MicroRNAs: Genomics, Biogenesis, Mechanism, and Function. Cell 116, 281–297.

Kemi OJ, P.M Haram, U. Wisloff, and O. Ellingsen. 2004. Aerobic fitness is associated with cardiomyocyte contractile capacity and endothelial function in exercise training and detraining. Circulation 109:2897–2904.

Pictures in order of citation





https://en.wikipedia.org/wiki/Heart#mediaviewer/File:Apikal4D.gif



Neri Serneri G.G., M. Boddi, P.A. Modesti, I. Cecioni, M. Coppo, L. Padeletti, A. Michelucci, A. Colella, and G. Galanti. 2001. Increased cardiac sympathetic activity and insulin-like growth factor-I formation are associated with physiological hypertrophy in athletes. Circulation Research 89:977–982.

Carè A., D. Catalucci, F. Felicetti, D. Bonci, A. Addario, P. Gallo, M.L. Bang, P. Segnalini, Y. Gu, N.D. Dalton, L. Elia, M.V.G. Latronico, M. Hoydal, C. Autore, M.A. Russo, G.W. Dorn, O. Ellingsen, P. Ruiz-Lozano, K.L Peterson, C.M. Croce, C. Peschle, and G. Condorelli. 2007. MicroRNA-133 controls cardiac hypertrophy. Nature Medicine 13: 613–618.

Kemi OJ, P.M Haram, U. Wisloff, and O. Ellingsen. 2004. Aerobic fitness is associated with cardiomyocyte contractile capacity and endothelial function in exercise training and detraining. Circulation 109:2897–2904.


http://i.imgur.com/8RVDB.jpg

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1 comment:

  1. Great job Kevin! This will help in studying for the final, too!

    ReplyDelete