Sho Edi o ial
The Impac O Exe cise On In lamma ion, Oxida i e S ess And
Remodelling In Ca diac Muscle
Fe nando Mendes1,2,3,4 and Diana Ma ins1,5
Poli écnico de Coimb a - Depa amen o de Ciências Biomédicas Labo a o iais ESTeSC,1 Coimb a – Po ugal
Consó cio CNC.IBILI/ Cen o de Biomedicina Ino ado a e Bio ecnologia (CIBB), Uni e sidade de Coimb a,2 Coimb a – Po ugal
Ins i u o de Bio ísica e Ins i u o de In es igação Clínica e Biomédica de Coimb a (iCBR) á ea de Meio Ambien e Gené ica e Oncobiologia
(CIMAGO), Faculdade de Medicina, Uni e sidade de Coimb a,3 Coimb a – Po ugal
Eu opean Associa ion o P o essions in Biomedical Sciences,4 B uxelles – Belgium
I3S, Ins i u o de In es igação e Ino ação em Saúde, Uni e sidade do Po o,5 Po o – Po ugal
Sho Edi o ial ela ed o he a icle: E ec s o Physical T aining on he Myoca dium o Oxa iec omized LDL Knockou Mice: MMP 2/9,
Collagen I/III, In lamma ion and Oxida i e S ess
Mailing Add ess: Fe nando Mendes •
Escola Supe io de Tecnologia da Saúde de Coimb a - Depa amen o de
Ciências Biomédicas Labo a o iais, Gabine e 1.9 - Rua 5 de Ou ub o - SM
Bispo - Apa ado 7006. Pos al Code 3046-854 Coimb a – Po ugal
E-mail: [email p o ec ed]
Keywo ds
Co ona y A e y Disease; Exe cise; Menopause;
Dyslipidemias; Physical ac i i y; Collagen; Oxida i e S ess;
In lamma ion; Mice.
DOI: h ps://doi.o g/10.36660/abc.20190735
Aging is na u ally connec ed wi h a decline, in some i no
all physiological unc ions, namely loss o bone mass densi y
(BMD) and s eng h associa ed wi h he loss o muscle mass.1-3
This muscle loss happens mainly due o an imbalance
be ween muscle p o ein syn hesis and muscle p o ein
b eakdown. The inc ease o ca abolic ac o s such as
oxida i e s ess and in lamma ion con ibu e signi ican ly o
he abo e p ocess. Ne e heless, he weakening o s eng h
and muscle loss is no linea , occu ing di e en ly in all sexes.
O he ac o s such as a decline in ho monal le els due o
menopause phenomenon a e hough o be also implica ed
in his p ocess.1 In ac , some au ho s p oposed ha , in
emales, an accele a ed loss o muscle mass and s eng h
a ises a an ea lie age han in males, a ound he ime o
menopause.1 A good body o e idence suppo s ha he
decline in muscle mass may be in line wi h he es ogen
dec ease ha ypi ies menopausal yea s.3
The p esen s udy published a A qui os B asilei os de
Ca diologia by B ianezi e al.4 p oposed o in es iga e he ae obic
exe cise aining on he le en icle in low-densi y lipop o ein
(LDL) knockou o a iec omized mice, mimicking he e ec s o
menopause, exe cise and i s e ec s on muscles o he mouse.
I is well known ha es ogen dec ease con ibu es o he
loss o BMD, as well as o he edis ibu ion o subcu aneous
a o he isce al a ea, associa ed o an inc eased isk o
ca dio ascula disease, a ec ing he quali y o li e o emales.
To wo sen he undesi able impac o menopause on emale’s
heal h, he dec ease in es ogen le els may also ha e a di ec
e ec on muscle issue.1,3
In o de o be e unde s and he abo e-men ioned
e ec s, Ledima e al.,4 design he ollowing expe imen ;
a g oup o hi y animals we e di ided in o 6 g oups,
each wi h 5 mice: non-o a iec omized seden a y con ol,
o a iec omized seden a y con ol, o a iec omized ained
con ol, non-o a iec omized seden a y LDL knockou ,
o a iec omized seden a y LDL knockou , o a iec omized
LDL knockou ained. The animals we e o a iec omized a
9 mon hs acco ding o he p o ocol desc ibed, a e ha he
animals we e exposed o wo di e en es s, one ega ding
he max aining es and a second one aining exe cises.
Then animals we e eu hanized and pa ame e s such as he
a e age olume densi y ype I and III collagen ib es, ma ix
me allop o einases (MMP) 2 and 9, oxida i e s ess (OS) we e
analysed. Thei esul s e ealed ha he exe cise p o ocol
al e ed he olume o collagen ib es in ype I and collagen
emodelling pa ame e s namely MMP-2, and u he educed
he OS pa ame e o 8-hyd oxy-2’-deoxyguanosine (8-OhdG).
In emales, aging o he ascula sys em only occu s due
o a decline o o a ian unc ion along wi h he decline in
associa ed ci cula ing ho mones, in pa icula es ogen.5
Al hough he isk ac o s, age and es ogen de iciency a e
well cha ac e ized, he mechanism o es ogen ac ion in he
ascula u e comp omised by aging a e no well de e mined.
In lamma ion is associa ed wi h he aging o he ascula
sys em, mainly due o he ele a ed le els o p oin lamma o y
cy okines, such as umou nec osis ac o (TNF), which
is also known o induce MMP. Fo example, MMP2 can
speci ically clea age big endo helin-1, sugges ing he ole
o his p o eoly ic enzyme in he ascula wall. Also, an
in e es ing s udy ound inc eased MMP2 ac i i y in he
mesen e ic a e ies om aged/es ogen-de icien animals,
which was es o ed when he animals we e ea ed wi h an
an i-in lamma o y agen a ge ing TNF.6 Also, he majo sou ce
o MMP-9 a e leucocy es, majo key playe s in in lamma o y
p ocess, sugges ing ha MMPs a e c i ical modula o s o
ascula disease in an aging/es ogen-de icien model.
Al hough es ogen eplacemen had been p oposed o
he managemen o ca dio ascula isk associa ed wi h aging
in emale, i s e icacy is con o e sial. Physical ac i i y seems
o be an e ec i e al e na i e o es ogen supplemen a ion
in pos -menopausal emales, imp o ing ae obic i ness and
physiological adap a ions o he ca dio ascula sys em.7-9
The e is some in iguing e idence ela ed o he loss
o es ogen in mice showing a ole in muscle con ac ile
p ope ies. Wohle s e al.10 s udied he con ac ile p ope ies
106
Sho Edi o ial
Mendes & Ma ins
E ec s o physical aining in emodelling, in lamma ion and oxida i e s ess
A q B as Ca diol. 2020; 114(1):106-108
o o a iec omized mice muscle, has demons a ed he lowe
capabili y o ac i a ing adenosine monophospha e kinase
(AMPK) phospho yla ion.10 This p o ein is impo an o glucose
up ake and lipid oxida ion in muscle, being implica ed in ene gy
p oduc ion, needed o p oduce muscle con ac ions.1,11,12
Associa ed o physical ac i i y is he gene a ion o eac i e
species o oxygen (ROS) ha may damage cell memb anes
lipids, p o eins as well as bo h mi ochond ial and nuclea
DNA in case o oxida i e s ess, ha can esul in se ious o
mo al cellula inju y.13,14
No ais e al.15 epo ed ha wi h eigh weeks o exe cise
aining in he ained hype ensi e menopausal g oup, ae obic
aining was e ec i e in p omo ing an inc ease in supe oxide
dismú ase (SOD) and ca alase, an ioxidan agen s, which ha e
a c ucial ole in oxida i e s ess modula ion. Also in animal
s udies, Claudio e al.16 demons a ed ha eigh weeks o
in e al aining p og ams signi ican ly inc eased SOD and
ca alase exp ession, con ibu ing o he educ ion o ca diac
supe oxide p oduc ion in a s wi h o a iec omized, in his case
wi h hype ension, which may p e en co ona y hea disease
in hype ensi e pos menopausal women.1,7,14
B ianezi e al.4 conclude ha mode a e-in ensi y ae obic
aining ac s on he olume o collagen ib es and on he
collagen emodelling, wi h educed oxida i e s ess in le
en icles o mice o a iec omized LDL Knockou . I is
known ha a e menopause, di e en ac o s con ibu e
o he decline in muscle mass, he combina ion o physical
inac i i y, p o ein in ake and oxida i e s ess16 clea ly
con ibu e he inc ease o his p ocess.16 Associa ed wi h he
oxida i e s ess inc ease, cha ac e ized by he imbalance
be ween he p oduc ion and he emo al o ee adicals,
usually due o an inadequa e an ioxidan sys em.16,17
Oxida i e s ess is ela ed o a highe ROS p oduc ion
om he mi ochond ia, which can induce cell apop osis.18
Meaning ha he mi ochond ial DNA may be damaged
due o oxida i e s ess, a ec ing mi ochond ia capaci y o
p oduce ene gy, con ibu ing o a highe suscep ibili y o
apop osis which inally in ensi ies muscle ib e a ophy o
dea h and muscle mass dec ease.1
Taking oge he , he esul s o B ianezie e al.4 conclude
ha physical exe cise con ibu es posi i ely in luencing he
con ol and dyslipidemic g oups in he pa ame e o densi y
and olume o collagen ib es o ype I and he con ol g oup
in ela ion o oxida i e s ess. The mechanisms unde lying
he pa hophysiology o menopausal al e a ions a e complex
and implica e es ogen-MMP-me abolic de egula ion wi h
age-d i en ascula changes.
Acknowledgemen s
Founda ion o Science and Technology (FCT), Po ugal
(S a egic P ojec s UID/NEU/04539/2013 and UID/
NEU/04539/2019), and COMPETE-FEDER (POCI-01-0145-
FEDER-007440).
1. Mal ais ML, Des oches J,Donne IJ. Changes in muscle mass and s eng h a e
enopause. J Musculoskele Neu onal In e ac . 2009;9(4):, 186–97.
2. Ca e CS, Jus ice JN,Thompson L. Lipo oxici y, aging, and muscle
con ac ili y: does ibe ype ma e ? Ge oScience.2019;41(3);297-308.
3. Calmels P, Vico L, Alexand e C, Minai e P. C oss-sec ional s udy o muscle
s eng h and bone mine al densi y in a popula ion o 106 women be ween
he ages o 44 and 87 yea s: ela ionship wi h age and menopause. Eu J
Appl Physiol Occup Physiol.1995;70(2):180-6.
4. B ianezi L, O nelas E, Geh ke FS, Fonseca LA, Al es BC, Sousa VA, e al.
E ei os do einamen o ísico sob e o miocá dio de camundongos LDL
Knocku o a iec omizadas: MMP -2c-9, Colageno I/II, in lamação e es esse
oxida i o. A q B as Ca diol. 2020; 114(1):100-105.
5. Lu be E, Ci ko a R, C uickshank JK, Dillon MJ, Fe ei a I, In i i C, e
al. Managemen o high blood p essu e in child en and adolescen s:
ecommenda ions o he Eu opean Socie y o Hype ension. J.
Hype ens.2009;27(2):1719-42.
6. Lekon se a O, Jiang Y, Da idg ST. Es ogen eplacemen inc eases ma ix
me allop o einase con ibu ion o asocons ic ion in a a model o
menopause. J Hype ens.2009;27(8):1602-8.
7. Lin YY, Lee SD. Ca dio ascula Bene i s o Exe cise T aining in
Pos menopausal Hype ension. In J Mol Sci.2018;9.pii e2523
8. Mye s J. Ca diology pa ien pages. Exe cise and ca dio ascula heal h.
Ci cula ion.2003;107(1):e2-5.
9. Faga d FH. Exe cise The apy in Hype ensi e Ca dio ascula Disease. P og
Ca dio asc Dis.2011;53(6):404-11.
10. Wohle s L M,Sweeney SM., Wa d CW, Lo e ing R M, Spangenbu g E E.
Changes in con ac ion-induced phospho yla ion o AMP-ac i a ed p o ein
kinase and mi ogen-ac i a ed p o ein kinases in skele al muscle a e
o a iec omy. J Cell Biochem. 2009; 107(1):171-8.
11. Jø gensen S B, Rich e E A, Woj aszewski J] F P. Role o AMPK in skele al
muscle me abolic egula ion and adap a ion in ela ion o exe cise. J
Physiol.2006;574(P 1):17-31.
12. Osle M E, Zie a h JR. Mini e iew: Adenosine 5’-Monophospha e-Ac i a ed
P o ein Kinase Regula ion o Fa y Acid Oxida ion in Skele al Muscle.
Endoc inology.2008;149(3):935-41.
13. Cheng TL,Lin YY, Su CT, Hu CC, Yang AL. Imp o emen o Ace ylcholine-
Induced Vasodila ion by Acu e Exe cise in O a iec omized Hype ensi e
Ra s. Chin J Physiol. 2016;59(3):165-72.
14. Claudio ER, Almeida SA, Mengal V, B asil GA, San uzzi CH, Ti aden es
RV. Swimming aining p e en s co ona y endo helial dys unc ion in
o a iec omized spon aneously hype ensi e a s. B az J Med Biol Res.
2017;50(1):e5495
15. No ais IP, Ja e e AP, Puga G, A aujo HN, Delbin MA, Zanesco A. E ec
o ae obic exe cise aining on GMP le els and blood p essu e in ea ed
hype ensi e pos menopausal women. Mo iz. 2017;23(1):1-6.
Re e ences
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Sho Edi o ial
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E ec s o physical aining in emodelling, in lamma ion and oxida i e s ess
A q B as Ca diol. 2020; 114(1):106-108
This is an open-access a icle dis ibu ed unde he e ms o he C ea i e Commons A ibu ion License
16. Signo elli S S,Ne i S, Sciacchi ano S, Pino LD, Cos a MP, Ma chese G, e al.
Beha iou o some indica o s o oxida i e s ess in pos menopausal and
e ile women. Ma u i as .2006;53(1):77-82.
17. Pansini F, Ce ella i C, Gua ien o A, S acchini MA, Cas aldini C, Be na di A,
e al. Oxida i e s ess, body a composi ion, and endoc ine s a us in p e- and
pos menopausal women. Menopause.2008;15(1):112-8.
18. Hiona A, The ole o mi ochond ial DNA mu a ions in aging and sa copenia:
Implica ions o he mi ochond ial icious cycle heo y o aging. Exp
Ge on ol.2008;43(1):24-33.
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