Physical Exercise Training and Chagas Disease: Potential Role of MicroRNAs

Improta-Caria, Alex Cleber; Aras Júnior, Roque

doi:10.36660/abc.20200330

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Review Article • Arq. Bras. Cardiol. 117 (1) • July 2021 • https://doi.org/10.36660/abc.20200330 linkcopy

Physical Exercise Training and Chagas Disease: Potential Role of MicroRNAs

Authorship SCIMAGO INSTITUTIONS RANKINGS

Chagas disease (CD) is caused by Trypanosoma Cruzi. This parasite can infect several organs of the human body, mainly the heart, causing inflammation, fibrosis, arrhythmias, and cardiac remodeling, promoting long-term Chronic Chagas Cardiomyopathy (CCC). However, little scientific evidence has elucidated the molecular mechanisms that govern the pathophysiological processes in this disease. MicroRNAs (miRNAs) are regulators of post-transcriptional gene expression that modulate signaling pathways, participating in pathophysiological mechanisms in CD, but the understanding of miRNAs in this disease is limited. On the other hand, a wide range of scientific evidence shows that physical exercise training (PET) modulates the expression of miRNAs by modifying different signaling pathways in healthy individuals. Some studies also show that PET is beneficial for individuals with CD; however, these did not evaluate the miRNA expressions. Thus, there is no evidence showing the role of PET in the expression of miRNAs in CD. Therefore, this review aimed to identify miRNAs expressed in CD that could potentially be modified by PET.

Exercise; Chagas Disease; MicroRNAs

MicroRNAs	Source	Findings	Reference
↓ miR-1, miR-133a, miR-133b, miR-208a, miR-208b	Heart samples	Association with connective tissue disorders and fibrosis	16
↑ miR-208b	Plasma samples	Association with cardiovascular dysfunction and myocardial hypertrophy	17
↑ miR-20, miR-20b, miR-21, miR-142, miR-146a, miR-146b, miR-155, miR-182, miR-203, miR-222 ↓ miR-139, miR-145, miR-149, miR-322, miR-503,	Heart samples	Association with heart rate-corrected QT (QTc) interval. Ventricular depolarization and repolarization.	14
↑ miR-19a, miR-21, miR-29b, miR-30a, miR-199b	Heart samples and cell model	Association with fibrosis and cardiac remodeling	18
↑ miR-16, miR-26b, miR-190b, miR-3586, let-7f-2 ↓ miR-190b	H9c2 cells, infected with T. Cruzi	Association with cell growth, hypertrophy, and cell survival	19

MicroRNAs	Target	Source	Types of Exercises	Reference
In vivo experimental models
↑ miR-27a, miR-155 ↓ miR-143	ACE, AT1R	Heart samples	Wistar-Kyoto rats Exercise training on treadmill	39
↑ miR-17-3p	TIMP-3 PTEN	Heart samples	C57Bl/6 mice Ramp swimming training model Voluntary wheel training	40
↑ miR-222	HIPK1	Heart samples	Ramp swimming model Voluntary wheel training	41
↑ miR-19b, miR-30e, miR-133b, miR-208a ↓ miR-99b, miR-100, miR-191a, miR-22, miR-181a	IGF-1 PI3K/AKT/mTOR MAPK	Heart samples Plasma	Wistar albino rats Swimming training	42
↑ miR-29a, miR-101a	TG-β fos COL1A1	Heart samples	Intermittent run exercise	43
↑ miR-27a, miR-27b ↓ miR-143	ACE ACE2	Heart samples	Wistar rats Swimming training	44
↑ miR-126	PI3KR2	Heart samples Plasma	Zucker rats Swimming training	26
↓ miR-214	SERCA2A	Heart samples	Wistar rats Resistance training	23
↑ miR-1 ↓ miR-214	NCX SERCA2A	Heart samples	Wistar rats Swimming training	27
↑ miR-29c ↓ miR-1, miR-133a, miR133b	COL1A1 COL3A1	Heart samples	Wistar rats Swimming training	45
↑ miR-126	SPRED1 PI3KR2	Heart samples	Wistar rats Swimming training	46
↑ miR-21, miR-144, miR-145 ↓ miR-124	PTEN PIK3A TSC2	Heart samples	Wistar rats Swimming training	20
↑ miR-336-5p, miR-130b-5p, let7d-3p, miR-466c-5p, miR-324-3p, miR-146b-5p, miR-132-3p, miR-21-5p, miR-187-3p, miR-29b-5p, miR-324-5p, miR-214-5p, miR-140-5p, miR-152-5p, miR-99b-5p, miR-130a-5p, miR-455-5p, miR-27b-3p, miR-23b-3p, miR-652-5p, miR-199a-3p, miR-223-5p, miR-421-3p, miR-27a-5p, miR-24-5p, miR-34a-3p, miR-140-3p, miR-125b-5p, miR-145a-5p, miR-192-5p, miR-139-5p, miR-199a-5p, miR-674-3p, miR-191-5p, miR-28-3p, miR-195-5p, miR-598, miR-429, miR-224, miR-425, miR-221 ↓ miR-701-5p, miR-220, miR-144-3p, miR-694, miR-485-3p, miR-136-5p, miR-384-3p, miR-376c-3p, miR-208b-3p, miR-411-3p, miR-141-5p, miR-1894-3p, miR-9a, miR-687, miR-451-5p	TNF-α COL1A1 MMP9 PTEN AKT1 AMPK BCL2	Heart samples	Wistar rats Aerobic run training	22
↑ miR-503, miR-465b-5p, miR-542-3p ↓ miR-652		Heart samples	C57Bl6 mice Swimming training	47
↓ miR-26b, miR-143	IGF1R GATA-4 NFAT1C GSK3B	Heart samples	Balb/c mice Aerobic metal wheels training	48
↑ miR-21, miR-30b ↓ miR-1	BCL-2 p53 PDCD4	Heart samples	Swimming training	49
↑ miR-23a, miR-27a	PTEN Casp7 FoxO1	Skeletal muscle samples	Resistance exercise	50
↑ miR-29c ↓ miR-1	COL1A1 COL3A1	Heart samples	Swimming training	51
↑ miR-382		Serum, tissues, and cell samples	IR mice Aerobic exercise	25
MicroRNAs	Targets	Source	Types of Exercises	Reference
Clinical studies
↑ miR-126, miR-133	CPK	Plasma	Single symptom-limited spiroergometry test Marathon run Eccentric resistance exercise	52
↓ miR-486	PTEN	Serum	Systematic-cycling at 70% VO2max	53
↑ miR-1, miR-126, miR-133a, miR-134, miR-146a, miR-208a, miR-499-5p	CPK NT-proBNP hsCRP	Plasma	Marathon run Immediately after run	21
↑ miR-1, miR-133a, miR-206, miR-208b, miR-499		Plasma	Marathon run Immediately after run	54
↑ miR-1, miR-133a, miR-206		Plasma	Marathon run Immediately after run	55
↑ let-7d-3p, let-7f-3p miR-29a-3p, miR-34a-5p, miR-125b-5pmiR-132-3p, miR-143-3p, miR-148a-3p, miR-223-3p, miR-223-5p miR-424-3p, miR-424-5p		Serum	Marathon run Immediately after run	56
↑ miR-1, miR-30a, miR-133a ↓ miR-26a, -29b		Plasma	Marathon run Immediately after run	57
↑ miR-1, miR-133a, miR-206		Plasma	Marathon run Immediately after run	58
↑ miR-1, miR-133a, miR-133b, miR-139-5p, miR-143, miR-145, miR-223, miR-330-3p, miR-338-3p, miR-424 ↓ miR-30b, miR-106a, miR-146, miR-151-3p, miR-151-5p, miR-221, miR-652, let-7i ↑ miR-103, miR-107 ↓ miR-21, miR-25, miR-29b, miR-92a, miR-133a, miR-148a, miR-148b, miR-185, miR-342-3p, miR-766, let-7d		Plasma	Cycle ergometry test 1-3 hs after exercise Systematic endurance cycle ergometry training	59
↑ miR-1, miR-133a, miR-133b, miR-206 miR-485-5p, miR-509-5p, miR-517a miR-518f, miR-520f, miR-522, miR-553, miR-888		Plasma	High intensity interval exercise Immediately after	60
↑ miR-181b, miR-214 ↑ miR-1, miR-133a, miR-133b, miR-208b		Plasma	Uphill treadmill test (concentric) Immediately after Downhill treadmill test (eccentric) 2-6 hs after exercise	61
↑ miR-149 ↓ miR-146a, miR-221		Serum	Resistance exercise 3 days after exercise	62
↑ miR-1, miR-133a, miR-133b, miR-206, miR-208b, miR-499		Plasma	Systematic resistance training 36-72 hs after training	63
↑ miR-1, miR-133a, miR-133b, miR-181a ↓ miR-9, miR-23a, miR-23b, miR-31 ↑ miR-1, miR-29b	HDAC4 NRF1	Skeletal muscle samples	Cycle ergometer, Cycling	64
↑ miR-136, miR-200c, miR-376a, miR-377, miR-499b, miR-558 ↓ miR-28, miR-30d, miR-204, miR-330, miR-345, miR-375, miR-449c, miR-483, miR-509, miR-520a, miR-548a, miR-628, miR-653, miR-670, miR-889, miR-1245a, miR-1270, miR-1280, miR-1322, miR-3180		Skeletal muscle samples	Resistance training	65
↑ miR-451 ↓ miR-26a, miR-29a, miR-378		Skeletal muscle samples	Resistance exercise	66
↑ miR-125a, miR-145, miR-181b, miR-193a, miR-197, miR-212, miR-223, miR-340, miR-365, miR-485, miR-505, miR-520d, miR-629, miR-638, miR-939, miR-940, miR-1225, miR-1238 ↓ let-7i, miR-16, miR-17, miR-18a, miR-18b, miR-20a, miR-20b, miR-22, miR-93, miR- 96, miR-106a, miR-107, miR-126, miR-130a, miR-130b, miR-151, miR-185, miR-194, miR-363, miR-660		Serum	Cycle ergometer exercise	67
↑ miR-7, miR-15a, miR-21, miR-26b, miR-132, miR-140, miR-181a, miR-181b, miR-181c, miR-338, miR-363, miR-939, miR-940, miR-1225 ↓ let-7e, miR-23b, miR-31, miR-99a, miR-125a, miR-125b, miR-126, miR-130a, miR-145, miR-151, miR-199a, miR-199b, miR-221, miR-320, miR-451, miR-486, miR-584, miR-652		PBMC	Cycle ergometer exercise	68
↑ let-7f, miR-21, miR-29c, miR-223 ↓ let-7f, miR-21, miR-29c, miR-223		PBMC	Running exercise	69
↑ miR-7, miR-29a, miR-29b, miR-29c, miR-30e, miR-142, miR-192, miR-338, miR-363, miR-590 ↓ let-7e, miR-126, miR-130a, miR-151, miR-199a, miR-221, miR-223, miR-326, miR-328, miR-652		PBMC	Cycle ergometer exercise	70
↑ miR-15a, miR-29b, miR-29c, miR-30e, miR-140, miR-324, miR-338, miR-362, miR-532, miR-660 ↓ miR-23b, miR-130a, miR-151, miR-199a, miR-221		Serum	Cycle ergometer exercise	71
↑ miR-1, miR-486, miR-494		Serum	(Endurance athletes, runners, cyclists, and triathletes) Cardiopulmonary exercise test	72
↑ miR-21, miR-146a, miR-221, miR-222 ↑ miR-20a, miR-21, miR-146a, miR-221, miR-222		Serum	Rowing training, 5Km, 1-3 h per session, 20-24 strokes/min)	73
↑ miR-376a ↓ miR-16, miR-27a, miR-28		Plasma	Aerobic run exercise training (4 days/week)	74
↑ miR-19a, miR-19b, miR-20a, miR-26b, miR-143, miR-195	p-AKT p-S6K1	Serum	Resistance exercise	75
↑ miR-222	HIPK1	Plasma	Bicycle Ergometry Test	41
↑ miR-221 ↓ miR-208b, miR-221, miR-21, miR-146a, miR-210		Serum	Basketball Exercise	76

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