Korean Circ J.  2018 Nov;48(11):1014-1024. 10.4070/kcj.2018.0084.

Exercise induced Right Ventricular Fibrosis is Associated with Myocardial Damage and Inflammation

• Rao Z
• Wang S
• Bunner WP
• Chang Y
• Shi R

• KMID: 2422550
• DOI: http://doi.org/10.4070/kcj.2018.0084

Abstract

BACKGROUND AND OBJECTIVES
Intense exercise (IE) induced myocardial fibrosis (MF) showed contradictory findings in human studies, making the relationship between IE and the development of MF unclear. This study aims to demonstrate exercise induced MF is associated with cardiac damage, and inflammation is essential to the development of exercise induced MF.
METHODS
Sprague-Dawley rats were submitted to daily 60-minutes treadmill exercise sessions at vigorous or moderate intensity, with 8-, 12-, and 16-week durations; time-matched sedentary rats served as controls. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum cardiac troponin I (cTnI) concentration. After completion of the exercise protocol rats were euthanized. Biventricular morphology, ultrastructure, and collagen deposition were then examined. Protein expression of interleukin (IL)-1β and monocyte chemotactic protein (MCP)-1 was evaluated in both ventricles.
RESULTS
After IE, right but not left ventricle (LV) MF occurred. Serum cTnI levels increased and right ventricular damage was observed at the ultrastructure level in rats that were subjected to long-term IE. Leukocyte infiltration into the right ventricle (RV) rather than LV was observed after long-term IE. Long-term IE also increased protein expression of pro-inflammation factors including IL-1β and MCP-1 in the RV.
CONCLUSIONS
Right ventricular damage induced by long-term IE is pathological and the following inflammatory response is essential to the development of exercise induced MF.

Keyword

Exercise; Fibrosis; Heart Ventricles; Heart injuries; Inflammation

MeSH Terms

Animals
Collagen
Enzyme-Linked Immunosorbent Assay
Fibrosis*
Heart Injuries
Heart Ventricles
Humans
Inflammation*
Interleukins
Leukocytes
Monocytes
Rats
Rats, Sprague-Dawley
Troponin I
Collagen
Interleukins
Troponin I

Figure

• 

  Figure 1 Picrosirius red staining (magnification ×400) and CVF of biventricular. MF occurred in RV rather than LV.CVF = collagen volume fraction; IE = intensive exercise; LV = left ventricle; ME = moderate exercise; MF = myocardial fibrosis; RV = right ventricle; Sed = sedentary.*p<0.05; **p<0.01.

• 

  Figure 2 Serum cTnI. Serum cTnI level increased after IE training.cTnI = cardiac troponin I; IE = intensive exercise; ME = moderate exercise; Sed = sedentary.**p<0.01.

• 

  Figure 3 Biventricular myocardial cells ultra-structural changes (magnification ×2,000). In the RV of IE rats: the number of mitochondria increased and mitochondria size showed heterogeneity; fibers appeared to be abnormally distorted and Z line blurred.IE = intensive exercise; LV = left ventricle; ME = moderate exercise; RV = right ventricle; Sed = sedentary.

• 

  Figure 4 Histological alterations of biventricular (H&E, magnification ×400). Myocyte in exercise (both ME and IE) rats are thicker than Sed rats. Myofibre disarray and disrupt existed in RV of IE rats. Occasional mononuclear inflammatory cells infiltration (arrow) showed in RV of 12 weeks and 16 weeks IE rats.H&E = hematoxylin and eosin; IE = intensive exercise; LV = left ventricle; ME = moderate exercise; RV = right ventricle; Sed = sedentary.

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  Figure 5 Relationship between right ventricular fibrosis and cardiac injury (r=0.597; p<0.001). Cardiac damage positive correlated with right ventricular fibrosis.cTnI = cardiac troponin I; CVF = collagen volume fraction; RV = right ventricle.

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  Figure 6 Proteins extracted from biventricular were assayed for levels of MCP-1 and IL-1β immunoblots, and immunoreactivating bands were quantified by densitometric analysis. Inflammation response was detected in RV rather than LV.GAPDH = glyceraldehyde 3-phosphate dehydrogenase; IE = intensive exercise; IL = interleukin; LV = left ventricle; MCP = monocyte chemotactic protein; ME = moderate exercise; RV = right ventricle; Sed = sedentary.*p<0.05.

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