Onorati Francesco, Forte Amalia, Mastroroberto Pasquale, Santè Pasquale, Esposito Salvatore, Pezzo Francesco, Agozzino Lucio, Cipollaro Marilena, Cascino Antonino, Renzulli Attilio
Cardiac Surgery Unit Magna Graecia University of Catanzaro, Cantanzaro, Italy.
J Surg Res. 2007 Dec;143(2):300-10. doi: 10.1016/j.jss.2006.11.026. Epub 2007 Aug 22.
Hypertension has been traditionally considered a risk factor for restenosis following carotid arteriotomy. Genetic and morphological response to carotid arteriotomy in normotensive Wystar-Kyoto (WKY), spontaneously hypertensive (SHR), and Milan hypertensive (MHS) rats were analyzed.
C-myc, angiotensin II receptor-1 (AT1), angiotensin II receptor-2 (AT2), endothelin-1 receptor A (ET(A)), endothelin-1 receptor B (ET(B)), Bcl-2 family-members (Bcl-2/Bax, Bcl-X(L/S)) were analyzed in surgically injured as well as uninjured carotids of WKY and hypertensive strains (HS). Thirty-day histology and morphometry were accomplished on injured and uninjured carotids.
C-myc mRNA is activated earlier and/or to a greater extent in hypertensive strains than in WKY. AT1 mRNA increases in WKY after injury, while it decreases in SHR and MHS. AT2 shows the opposite, decreasing in WKY and increasing in hypertensive strains. ET(A) mRNA decreases in all strains although with different timing and levels, associated with a replacement by ET(B) mRNA. Bcl-2/Bax ratio gradually decreases in WKY, while it shows only a transient decrease in SHR and MHS 4 h after the injury. Negative remodeling is observed in all injured carotids, although neointima was detected in WKY only. Thirty days following arteriotomy, morphometry demonstrated a significant decrease of luminal area, with consistent gain in the medial area in WKY, whereas hypertensive strains showed significant increase of the luminal area, consistent with a contemporary decrease of the medial area.
Vaso-relaxant AT2 and ET(B) induced limited vasoconstriction in HS. Less apoptosis in hypertensive rats reduced cell proliferation, contrasting c-myc. These responses favorably modulated media/lumen area ratio following arteriotomy in HS.
传统上认为高血压是颈动脉切开术后再狭窄的一个危险因素。分析了正常血压的威斯塔-京都（WKY）大鼠、自发性高血压（SHR）大鼠和米兰高血压（MHS）大鼠对颈动脉切开术的基因和形态学反应。
分析了WKY大鼠和高血压品系（HS）手术损伤及未损伤颈动脉中的C-myc、血管紧张素II受体-1（AT1）、血管紧张素II受体-2（AT2）、内皮素-1受体A（ET(A)）、内皮素-1受体B（ET(B)）、Bcl-2家族成员（Bcl-2/Bax、Bcl-X(L/S)）。对损伤和未损伤的颈动脉进行了30天的组织学和形态学测量。
与WKY大鼠相比，C-myc mRNA在高血压品系中更早和/或更大程度地被激活。WKY大鼠损伤后AT1 mRNA增加，而SHR和MHS大鼠中则减少。AT2表现出相反的情况，在WKY大鼠中减少，在高血压品系中增加。ET(A) mRNA在所有品系中均减少，尽管时间和水平不同，同时伴随着ET(B) mRNA的替代。WKY大鼠中Bcl-2/Bax比值逐渐降低，而SHR和MHS大鼠在损伤后4小时仅出现短暂降低。所有损伤的颈动脉均观察到负性重塑，不过仅在WKY大鼠中检测到新生内膜。动脉切开术后30天，形态学测量显示管腔面积显著减小，WKY大鼠中膜面积持续增加，而高血压品系的管腔面积显著增加，同时中膜面积减小。
血管舒张性的AT2和ET(B)在高血压品系中诱导有限的血管收缩。高血压大鼠中较少的细胞凋亡减少了细胞增殖，与c-myc相反。这些反应在高血压品系动脉切开术后对中膜/管腔面积比值产生了有利的调节作用。
