Gene expression and morphological changes in surgically injured carotids of spontaneously hypertensive rats.
The expression profiles of genes involved in cell proliferation, differentiation and programmed death were investigated in carotids of spontaneously hypertensive rats (SHR) treated with a model of surgical injury that mimics events occurring during arterial grafts, endarterectomy and organ transplantation. The mRNA level of the c-myc, angiotensin II receptor 1 (AT1), Rb/p105, Rb2/p130, Bcl-2 and Bax-alpha genes was assessed by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) technique at different times up to 48 h after injury, while the morphological changes were evaluated 30 days after injury. The proliferation marker c-myc increases almost immediately, peaks after 4 h and returns to basal levels after 24 h; the AT1 receptor mRNA reaches its maximal level 48 h after injury. The level of cell cycle exit markers Rb/p105 and Rb2/p130 gradually decreases after injury. The apoptosis marker Bcl-2/Bax-alpha ratio shows a significant reduction only 4 h after injury, resuming the initial value after 24 and 48 h. Morphological analysis reveals that surgical injury in SHR induces adventitial and medial constrictive remodeling changes rather than intima proliferation as in balloon angioplasty. Both molecular and histological data show substantial differences with respect to normotensive rats.
Forte
A
A
Research Center for Cardiovascular Diseases, Department of Experimental Medicine, Second University of Naples, Italy.
Di Micco
G
G
Galderisi
U
U
De Feo
M
M
Esposito
F
F
Esposito
S
S
Renzulli
A
A
Berrino
L
L
Cipollaro
M
M
Agozzino
L
L
Cotrufo
M
M
Rossi
F
F
Cascino
A
A
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D020212:Carotid Artery Injuries / Q000378:metabolism* / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D015870:Gene Expression; D016259:Genes, myc; D006973:Hypertension / Q000473:pathology*; D007431:Intraoperative Complications; D007700:Kinetics; D008297:Male; D010750:Phosphoproteins / Q000235:genetics; D011506:Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000235:genetics; D016160:Retinoblastoma Protein / Q000235:genetics; D050717:Retinoblastoma-Like Protein p130; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C493839:Rbl2 protein, rat; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D016160:Retinoblastoma Protein; D050717:Retinoblastoma-Like Protein p130; D051028:bcl-2-Associated X Protein