Stenosis progression after surgical injury in Milan hypertensive rat carotid arteries.
BACKGROUND
Milan hypertensive rats (MHS) are characterised by an increase in renal sodium reabsorption mainly related to adducin mutations. Interest in this model relies on the genetic link between adducin polymorphisms and primary hypertension, observed also in a subset of patients.


OBJECTIVE
To investigate the molecular and morphological events involved in carotid stenosis and triggered by surgery in MHS model.


METHODS
Stenosis was induced through arteriotomy. At different times after injury, the expression profiles of various gene families were investigated by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), while histological techniques were used to follow morphometric and morphological changes. Apoptotic nuclei were revealed by terminal deoxynucleotidyl transferase-dUTP nick end labelling (TUNEL).


RESULTS
mRNAs coding for transcription factors c-jun, c-fos and c-myc were rapidly induced by injury. Analysis of apoptosis-related genes revealed a decrease of the Bcl-2/Bax ratio 4 h after vascular trauma (P<0.05), followed by a recovery of antiapoptotic factors 24 and 48 h later. ET(A) and receptor mRNAs decreased after the injury and were replaced by ET(B) and AT2 mRNAs. Both ET(A) and AT1 turned to basal level 48 h after injury. Expression profiles of chatepsins B and D were also determined. A marked neoadventitia led to maximal 60+/-9% lumen reduction (P<0.05) 30 days after surgery. Media substitution by fibrotic and granulomatous tissue was also evident. Maximal 47+/-2% apoptotic nuclei were detected 48 h after the injury (P<0.05).


CONCLUSIONS
The injury applied to MHS carotids induces negative remodelling and a limited apoptotic reaction. These findings could arise from the balancing among proliferative factors, apoptosis-related molecules and relaxant anti-proliferative receptors, all stimulated by the injury.
Forte
Amalia
A
Department of Experimental Medicine, Second University of Naples, Via Costantinopoli, 16, 80138 Naples, Italy. amalia.forte@unina2.it
Esposito
Salvatore
S
De Feo
Marisa
M
Galderisi
Umberto
U
Quarto
Cesare
C
Esposito
Ferdinando
F
Renzulli
Attilio
A
Berrino
Liberato
L
Cipollaro
Marilena
M
Agozzino
Lucio
L
Cotrufo
Maurizio
M
Rossi
Francesco
F
Cascino
Antonino
A
D000803:Angiotensin I / Q000235:genetics; D000804:Angiotensin II / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D002339:Carotid Arteries / Q000378:metabolism* / Q000473:pathology; D016893:Carotid Stenosis / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D015870:Gene Expression; D016762:Genes, fos; D016758:Genes, jun; D016259:Genes, myc; D006973:Hypertension / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D023421:Models, Animal; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D044022:Receptor, Endothelin A / Q000235:genetics; D044023:Receptor, Endothelin B / Q000235:genetics
D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D000804:Angiotensin II; D000803:Angiotensin I