The effect of fructose rich diet on the expression of renin-angiostensin system components and inflamatory molecules in the rat heart: sex specific differences
Ishrana bogata fruktozom predstavlja bitan faktor u razvoju metaboličkog
sindroma koji je povezan sa povećanim rizikom za nastanak kardiovaskularnih bolesti.
Smatra se da hronična inflamacija ima bitnu ulogu u njegovoj patogenezi. Ženke su
zaštićene od ishranom izazvanih metaboličkih poremećaja i hipertenzije u
reproduktivnom periodu. Estrogen, koji utiče na normalno funkcionisanje
kardiovaskularnog sistema, bi mogao doprinositi uočenim polno specifičnim razlikama u
nastanku simptoma metaboličkog sindroma. Proteinske komponente renin-angiotenzin
sistema (RAS) imaju bitnu ulogu u nastanku inflamacije, hipertenzije i insulinske
rezistencije i na njihovu ekspresiju utiče estradiol. Ova doktorska disertacija je za cilj
imala da ispita da li pol i estradiol doprinose promenama u ekspresiji komponenti RAS-a
[angiotenzin konvertujućeg enzima (ACE), angiotenzin konvertujućeg enzima 2 (ACE2),
angiotenzinskog receptora tipa 1 (AT1R), angiotenzinskog receptora tipa 2 (AT2R) i
kolektrina] i medijatora inflamacije i remodelovanja tkiva srca [nuklearnog faktora κB
(NFκB), matriks metaloproteinaze-9 (MMP-9) i liganda 16 iz familije hemokina CXC
(CXCL16)] kod animalnog modela metaboličkog sindroma.
Mužjaci i ženke pacova koji su pili 10% rastvor fruktoze umesto vode u trajanju
od 9 nedelja predstavljali su animalni model metaboličkog sindroma korišćen u ovoj
studiji. Radi ispitivanja efekata estradiola jedan deo ženki pacova je ovarijektomisan i
podeljen u tri grupe pri čemi je jedna grupa pored standardne laboratorijske hrane pila
vodu, druga grupa je pila 10% rastvor fruktoze, a treća grupa je pored rasvora fruktoze
primala i supstitucionu terapiju estradiolom. Ishrana bogata fruktozom je uzrokovala
povećanje krvnog pritiska samo kod mužjaka pacova. Ovaj tip ishrane nije doveo do
promena u masi srca niti u odnosu masa srca/masa tela ni kod jednog pola, kao ni kod
ovarijektomisanih životinja što ukazuje da se hipertrofija srca nije razvila...Fructose rich diet (FRD) represents an important factor in the development of
metabolic syndrome. Metabolic syndrome is associated with increased risk for
cardiovascular diseases occurrence and chronic inflammation has a major role in its
pathogenesis. Females are protected from diet-induced metabolic disturbances and
hypertension in their reproductive period. Estrogen, which influences the cardiovascular
system, could contribute to the observed gender-specific differences in the onset of
metabolic syndrome. Components of the renin-angiotensin system (RAS), the synthesis
of which is mediated by estrogen, have an important role in the inflammatory processes,
hypertension and insulin resistance. Almost all of the components of metabolic syndrome
increase the activity of RAS, which finally results in increased oxidative stress and
inflammation. The aim of this doctoral dissertation was to investigate sex specific changes
and role of estradiol in the expression of RAS components [angiotensin converting
enzyme (ACE), angiotensin converting enzyme 2 (ACE2), angiotensin receptor type 1
(AT1R), angiotensin receptor type 2 (AT2R) and collectrin], as well as mediators of
inflammation and remodeling of heart tissue [nuclear faktor κB (NFκB), matrix
metalloproteinse-9 (MMP-9) and CXCL16 chemokine] in the animal model of metabolic
syndrome.
Male and female rats, which consumed 10% fructose solution instead of water for
9 weeks, represent an animal model of metabolic syndrome that was used in this study. In
order to examine the effects of estradiol in the context of FRD, female rats were
ovariectomized and divided in three groups: fed normal diet, fed FRD, and fed FRD and
subjected to estradiol replacement therapy. FRD increased blood pressure only in male
rats. This diet regime didn't cause heart hypertrophy neither in intact males and females,
nor in ovariectomized females..
