The expression of renin-angiotensin system components in human carotid plaque
Ekspresija komponenti renin-angiotenzin sistema u humanom karotidnom plaku
Апстракт
Background/Aim. The renin-angiotensin system (RAS) is linked to the development of atherosclerosis (As), including its initiation and progression. Besides the well-known angio-tensin-converting enzyme (ACE), two newer RAS family members are related to vascular remodeling - ACE2 as a homolog of ACE and collectrin [transmembrane protein 27 (TMEM27)] as a homolog of ACE2. Up to now, a limited number of studies have examined the expression of these RAS components in advanced carotid plaque (CP) tissue based on the sex of the patients and plaque phenotypes (PPs). There are two ultrasonographically defined PPs - the hypoechogenic plaque (HoP) and the hyperechogenic plaque (HerP) phenotype. The aim of the study was to investigate whether there was a correlation between the expression of RAS components in the CP and the sex and PPs of patients. Methods. We examined 74 patients with advanced CP who underwent carotid endarterectomy. The intraplaque expression of RAS components was determined wit...h the real-time polymerase chain reaction, using the TaqMan® gene expression assays and Western blot. A two-way ANOVA followed by a post-hoc Tukey test was performed for the statistical analysis of results. Results. No interaction was recorded between the sex of the patients and PPs in influencing the relative expression of ACE and TMEM27 messenger RNA (mRNA) (p > 0.05). In 56.06% of plaque samples, no expression of ACE2 mRNA was detected. Among the plaques where ACE2 mRNA expression was detected, its expression level was higher in females with the HoP phenotype compared to females with the HerP phenotype (p < 0.001). In patients with the HoP phenotype, females had higher expression of ACE2 mRNA than males (p < 0.05). In the male study group, ACE protein levels were significantly lower in the HoP phenotype compared to the HerP phenotype (p < 0.001). Fe-males with the HoP phenotype had significantly higher ACE protein levels than males with the HoP phenotype (p < 0.0001). Conclusion. Our results revealed alterations in the expression levels of ACE and ACE2, at the mRNA and protein levels, in advanced carotid As. These alterations are impacted by sex and PP and may indicate a switch from the balanced RAS/ACE/ACE2 axis in the healthy blood vessel to the unbalanced axis in vascular remodeling due to As.
Renin-angiotenzin sistem (RAS) povezan je sa
razvojem ateroskleroze (As), uključujući njen nastanak i
progresiju. Pored dobro poznatog angiotenzinkonvertujućeg enzima (angiotensin-converting enzyme – ACE),
dva nova člana RAS familije povezana su sa
remodelovanjem zidova krvnih sudova – ACE2 kao
homolog ACE i kolektrin [transmembrane protein 27
(TMEM27)] kao homolog ACE2. Do sada je mali broj
studija ispitivao ekspresiju komponenti RAS sistema u tkivu
uznapredovalog karotidnog plaka (KP) u odnosu na pol
bolesnika i fenotip plaka (FP). Postoje dva tipa KP
definisana primenom ultrazvuka – fenotip hipoehogenog
plaka (HoP) i fenotip hiperehogenog plaka (HerP). Cilj rada
bio je da se ispita da li postoji korelacija između ekspresije
komponenti RAS u KP i pola i FP bolesnika. Metode.
Ispitano je 74 bolesnika sa uznapredovalim KP koji su bili
podvrgnuti operativnoj proceduri karotidne
endarterektomije. Ekspresija komponenti RAS sistema u
tkivu plaka utvrđena je lančanom reakci...jom polimeraze u
realnom vremenu (real-time polymerase chain reaction)primenom eseja TaqMan® tehnologije i metode Western blota. Dvosmerna analiza varijanse i Tukey post-hoc test korišćen su za statističku obradu rezultata. Rezultati. Nije utvrđena
interakcija FP i pola bolesnika u uticaju na relativnu
ekspresiju informacione RNK (iRNK) za ACE i TMEM27
(p > 0,05). U 56,06% uzoraka plaka nije detektovana
ekspresija iRNK za ACE2. U plakovima u kojima je
detektovana ekspresija iRNK za ACE2, njen nivo bio je viši
kod žena sa HoP u poređenju sa ženama sa HerP (p <
0,001). U grupi bolesnika sa fenotipom HoP, žene su imale
viši nivo iRNK za ACE2 nego muškarci (p < 0,05). U grupi
muškaraca, nivoi ekspresije ACE proteina bili suznačajno
niži u fenotipu HoP u poređenju sa HerP (p < 0,001). Žene
sa fenotipom HoP imale su značajno viši nivo ACE
proteina u poređenju sa muškarcima sa HoP (p < 0,0001).
Zaključak. Naši rezultati pokazali su da postoje promene
nivoa ekspresije ACE i ACE2, na nivou proteina i iRNK u
uznapredovaloj karotidnoj As. Te promene zavise od pola i
FP i mogu ukazivati na to da balans ose RAS/ACE/ACE2
koji postoji u zdravom krvnom sudu postaje poremećen
tokom remodelovanja zida krvnog suda usled As.
Кључне речи:
carotid artery diseases / gene expression / plaque / atherosclerotic / proteins / renin angiotensin system / RNA / messenger / carotid artery diseases / gene expression / plaque / atherosclerotic / proteins / renin angiotensin system / rna / messenger / aa.carotis / bolesti / geni / ekspresija / aterosklerotički plak / proteini / renin-angiotenzin sistem / rnk / informacionaИзвор:
Vojnosanitetski pregled, 2024, 81, 4, 231-241Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200017 (Универзитет у Београду, Институт за нуклеарне науке Винча, Београд-Винча) (RS-MESTD-inst-2020-200017)
Колекције
Институција/група
VinčaTY - JOUR AU - Kolaković, Ana AU - Bundalo, Maja AU - Đurić, Tamara AU - Končar, Igor AU - Stanković, Aleksandra AU - Živković, Maja PY - 2024 UR - https://vinar.vin.bg.ac.rs/handle/123456789/13103 AB - Background/Aim. The renin-angiotensin system (RAS) is linked to the development of atherosclerosis (As), including its initiation and progression. Besides the well-known angio-tensin-converting enzyme (ACE), two newer RAS family members are related to vascular remodeling - ACE2 as a homolog of ACE and collectrin [transmembrane protein 27 (TMEM27)] as a homolog of ACE2. Up to now, a limited number of studies have examined the expression of these RAS components in advanced carotid plaque (CP) tissue based on the sex of the patients and plaque phenotypes (PPs). There are two ultrasonographically defined PPs - the hypoechogenic plaque (HoP) and the hyperechogenic plaque (HerP) phenotype. The aim of the study was to investigate whether there was a correlation between the expression of RAS components in the CP and the sex and PPs of patients. Methods. We examined 74 patients with advanced CP who underwent carotid endarterectomy. The intraplaque expression of RAS components was determined with the real-time polymerase chain reaction, using the TaqMan® gene expression assays and Western blot. A two-way ANOVA followed by a post-hoc Tukey test was performed for the statistical analysis of results. Results. No interaction was recorded between the sex of the patients and PPs in influencing the relative expression of ACE and TMEM27 messenger RNA (mRNA) (p > 0.05). In 56.06% of plaque samples, no expression of ACE2 mRNA was detected. Among the plaques where ACE2 mRNA expression was detected, its expression level was higher in females with the HoP phenotype compared to females with the HerP phenotype (p < 0.001). In patients with the HoP phenotype, females had higher expression of ACE2 mRNA than males (p < 0.05). In the male study group, ACE protein levels were significantly lower in the HoP phenotype compared to the HerP phenotype (p < 0.001). Fe-males with the HoP phenotype had significantly higher ACE protein levels than males with the HoP phenotype (p < 0.0001). Conclusion. Our results revealed alterations in the expression levels of ACE and ACE2, at the mRNA and protein levels, in advanced carotid As. These alterations are impacted by sex and PP and may indicate a switch from the balanced RAS/ACE/ACE2 axis in the healthy blood vessel to the unbalanced axis in vascular remodeling due to As. AB - Renin-angiotenzin sistem (RAS) povezan je sa razvojem ateroskleroze (As), uključujući njen nastanak i progresiju. Pored dobro poznatog angiotenzinkonvertujućeg enzima (angiotensin-converting enzyme – ACE), dva nova člana RAS familije povezana su sa remodelovanjem zidova krvnih sudova – ACE2 kao homolog ACE i kolektrin [transmembrane protein 27 (TMEM27)] kao homolog ACE2. Do sada je mali broj studija ispitivao ekspresiju komponenti RAS sistema u tkivu uznapredovalog karotidnog plaka (KP) u odnosu na pol bolesnika i fenotip plaka (FP). Postoje dva tipa KP definisana primenom ultrazvuka – fenotip hipoehogenog plaka (HoP) i fenotip hiperehogenog plaka (HerP). Cilj rada bio je da se ispita da li postoji korelacija između ekspresije komponenti RAS u KP i pola i FP bolesnika. Metode. Ispitano je 74 bolesnika sa uznapredovalim KP koji su bili podvrgnuti operativnoj proceduri karotidne endarterektomije. Ekspresija komponenti RAS sistema u tkivu plaka utvrđena je lančanom reakcijom polimeraze u realnom vremenu (real-time polymerase chain reaction)primenom eseja TaqMan® tehnologije i metode Western blota. Dvosmerna analiza varijanse i Tukey post-hoc test korišćen su za statističku obradu rezultata. Rezultati. Nije utvrđena interakcija FP i pola bolesnika u uticaju na relativnu ekspresiju informacione RNK (iRNK) za ACE i TMEM27 (p > 0,05). U 56,06% uzoraka plaka nije detektovana ekspresija iRNK za ACE2. U plakovima u kojima je detektovana ekspresija iRNK za ACE2, njen nivo bio je viši kod žena sa HoP u poređenju sa ženama sa HerP (p < 0,001). U grupi bolesnika sa fenotipom HoP, žene su imale viši nivo iRNK za ACE2 nego muškarci (p < 0,05). U grupi muškaraca, nivoi ekspresije ACE proteina bili suznačajno niži u fenotipu HoP u poređenju sa HerP (p < 0,001). Žene sa fenotipom HoP imale su značajno viši nivo ACE proteina u poređenju sa muškarcima sa HoP (p < 0,0001). Zaključak. Naši rezultati pokazali su da postoje promene nivoa ekspresije ACE i ACE2, na nivou proteina i iRNK u uznapredovaloj karotidnoj As. Te promene zavise od pola i FP i mogu ukazivati na to da balans ose RAS/ACE/ACE2 koji postoji u zdravom krvnom sudu postaje poremećen tokom remodelovanja zida krvnog suda usled As. T2 - Vojnosanitetski pregled T1 - The expression of renin-angiotensin system components in human carotid plaque T1 - Ekspresija komponenti renin-angiotenzin sistema u humanom karotidnom plaku VL - 81 IS - 4 SP - 231 EP - 241 DO - 10.2298/VSP221028014K ER -
@article{ author = "Kolaković, Ana and Bundalo, Maja and Đurić, Tamara and Končar, Igor and Stanković, Aleksandra and Živković, Maja", year = "2024", abstract = "Background/Aim. The renin-angiotensin system (RAS) is linked to the development of atherosclerosis (As), including its initiation and progression. Besides the well-known angio-tensin-converting enzyme (ACE), two newer RAS family members are related to vascular remodeling - ACE2 as a homolog of ACE and collectrin [transmembrane protein 27 (TMEM27)] as a homolog of ACE2. Up to now, a limited number of studies have examined the expression of these RAS components in advanced carotid plaque (CP) tissue based on the sex of the patients and plaque phenotypes (PPs). There are two ultrasonographically defined PPs - the hypoechogenic plaque (HoP) and the hyperechogenic plaque (HerP) phenotype. The aim of the study was to investigate whether there was a correlation between the expression of RAS components in the CP and the sex and PPs of patients. Methods. We examined 74 patients with advanced CP who underwent carotid endarterectomy. The intraplaque expression of RAS components was determined with the real-time polymerase chain reaction, using the TaqMan® gene expression assays and Western blot. A two-way ANOVA followed by a post-hoc Tukey test was performed for the statistical analysis of results. Results. No interaction was recorded between the sex of the patients and PPs in influencing the relative expression of ACE and TMEM27 messenger RNA (mRNA) (p > 0.05). In 56.06% of plaque samples, no expression of ACE2 mRNA was detected. Among the plaques where ACE2 mRNA expression was detected, its expression level was higher in females with the HoP phenotype compared to females with the HerP phenotype (p < 0.001). In patients with the HoP phenotype, females had higher expression of ACE2 mRNA than males (p < 0.05). In the male study group, ACE protein levels were significantly lower in the HoP phenotype compared to the HerP phenotype (p < 0.001). Fe-males with the HoP phenotype had significantly higher ACE protein levels than males with the HoP phenotype (p < 0.0001). Conclusion. Our results revealed alterations in the expression levels of ACE and ACE2, at the mRNA and protein levels, in advanced carotid As. These alterations are impacted by sex and PP and may indicate a switch from the balanced RAS/ACE/ACE2 axis in the healthy blood vessel to the unbalanced axis in vascular remodeling due to As., Renin-angiotenzin sistem (RAS) povezan je sa razvojem ateroskleroze (As), uključujući njen nastanak i progresiju. Pored dobro poznatog angiotenzinkonvertujućeg enzima (angiotensin-converting enzyme – ACE), dva nova člana RAS familije povezana su sa remodelovanjem zidova krvnih sudova – ACE2 kao homolog ACE i kolektrin [transmembrane protein 27 (TMEM27)] kao homolog ACE2. Do sada je mali broj studija ispitivao ekspresiju komponenti RAS sistema u tkivu uznapredovalog karotidnog plaka (KP) u odnosu na pol bolesnika i fenotip plaka (FP). Postoje dva tipa KP definisana primenom ultrazvuka – fenotip hipoehogenog plaka (HoP) i fenotip hiperehogenog plaka (HerP). Cilj rada bio je da se ispita da li postoji korelacija između ekspresije komponenti RAS u KP i pola i FP bolesnika. Metode. Ispitano je 74 bolesnika sa uznapredovalim KP koji su bili podvrgnuti operativnoj proceduri karotidne endarterektomije. Ekspresija komponenti RAS sistema u tkivu plaka utvrđena je lančanom reakcijom polimeraze u realnom vremenu (real-time polymerase chain reaction)primenom eseja TaqMan® tehnologije i metode Western blota. Dvosmerna analiza varijanse i Tukey post-hoc test korišćen su za statističku obradu rezultata. Rezultati. Nije utvrđena interakcija FP i pola bolesnika u uticaju na relativnu ekspresiju informacione RNK (iRNK) za ACE i TMEM27 (p > 0,05). U 56,06% uzoraka plaka nije detektovana ekspresija iRNK za ACE2. U plakovima u kojima je detektovana ekspresija iRNK za ACE2, njen nivo bio je viši kod žena sa HoP u poređenju sa ženama sa HerP (p < 0,001). U grupi bolesnika sa fenotipom HoP, žene su imale viši nivo iRNK za ACE2 nego muškarci (p < 0,05). U grupi muškaraca, nivoi ekspresije ACE proteina bili suznačajno niži u fenotipu HoP u poređenju sa HerP (p < 0,001). Žene sa fenotipom HoP imale su značajno viši nivo ACE proteina u poređenju sa muškarcima sa HoP (p < 0,0001). Zaključak. Naši rezultati pokazali su da postoje promene nivoa ekspresije ACE i ACE2, na nivou proteina i iRNK u uznapredovaloj karotidnoj As. Te promene zavise od pola i FP i mogu ukazivati na to da balans ose RAS/ACE/ACE2 koji postoji u zdravom krvnom sudu postaje poremećen tokom remodelovanja zida krvnog suda usled As.", journal = "Vojnosanitetski pregled", title = "The expression of renin-angiotensin system components in human carotid plaque, Ekspresija komponenti renin-angiotenzin sistema u humanom karotidnom plaku", volume = "81", number = "4", pages = "231-241", doi = "10.2298/VSP221028014K" }
Kolaković, A., Bundalo, M., Đurić, T., Končar, I., Stanković, A.,& Živković, M.. (2024). The expression of renin-angiotensin system components in human carotid plaque. in Vojnosanitetski pregled, 81(4), 231-241. https://doi.org/10.2298/VSP221028014K
Kolaković A, Bundalo M, Đurić T, Končar I, Stanković A, Živković M. The expression of renin-angiotensin system components in human carotid plaque. in Vojnosanitetski pregled. 2024;81(4):231-241. doi:10.2298/VSP221028014K .
Kolaković, Ana, Bundalo, Maja, Đurić, Tamara, Končar, Igor, Stanković, Aleksandra, Živković, Maja, "The expression of renin-angiotensin system components in human carotid plaque" in Vojnosanitetski pregled, 81, no. 4 (2024):231-241, https://doi.org/10.2298/VSP221028014K . .
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