Suguru Shiraya

Inhibition of development of experimental aortic abdominal aneurysm in rat model by atorvastatin through inhibition of macrophage migration

Recently, atherosclerosis has been considered to be the result of inflammation. Interestingly, hydroxymethylglutaryl-coenzyme (HMG-Co) A inhibitors (statins), which are clinically used as lipid-lowering agents, have been reported to have various anti-inflammatory effects. As abdominal aortic aneurysm (AAA) is a common degenerative condition associated with atherosclerosis, this study was designed to investigate the inhibitory effect of a statin, atorvastatin, on aneurysm formation apart from its lipid-lowering effect. We employed an elastase-induced rat AAA model, as statins do not lower cholesterol in rats. Mean aneurysm diameter was significantly smaller in the atorvastatin treatment group as compared to control at 4 weeks after surgery (P<0.05). Interestingly, atorvastatin inhibited the expression of ICAM and MCP-1, followed by the suppression of macrophage recruitment into the aortic wall at 1 week after operation. A significant reduction in MMP-12, but not MMP-2, -3 and -9, expression was also observed by treatment with atorvastatin at 1 week after surgery. In addition, synthesis of collagen and elastin in the vascular wall were significantly increased by atorvastatin. Here, the present study demonstrated a direct effect of atorvastatin to inhibit the progression of aortic aneurysm, independent of its lipid-lowering effect. This study suggests new therapeutic aspects of statins to inhibit the progression of aneurysms.

Hypertension Accelerated Experimental Abdominal Aortic Aneurysm Through Upregulation of Nuclear Factor κB and Ets

In this study, we focused on the effect of hypertension on the transcription factors nuclear factor &kgr;B (NF&kgr;B) and ets in the mechanisms of abdominal aortic aneurysm (AAA), and we investigated how hypertension affects the progression of AAA. AAA was produced by elastase perfusion in hypertensive rats and normotensive rats. The size of AAA rapidly increased in hypertensive rats as compared with normotensive rats. Western blot analysis demonstrated that the expression of matrix metalloproteinase (MMP)-2, -3, -9, and -12, as well as intercellular adhesion molecule, was increased in hypertensive AAA rats, accompanied by upregulation of NF&kgr;B and ets. Moreover, in situ zymography showed that the activity of MMPs was increased in the aorta of a hypertensive AAA model as compared with that in a normotensive AAA model. Interestingly, transfection of chimeric decoy oligodeoxynucleotide (ODN) resulted in significant inhibition of aortic dilatation both in normotensive and hypertensive rats at 4 weeks after transfection. Destruction of elastic fibers was also significantly inhibited by transfection of chimeric decoy ODN in both hypertensive rats and normotensive rats. The expression of MMP-2, -3, -9, and -12, as well as intercellular adhesion molecule, was significantly attenuated by the chimeric decoy ODN, accompanied by inhibition of the migration of macrophages. Also, the effect of chimeric decoy ODN was confirmed in an organ culture. The present study demonstrated that hypertension accelerated the progression of experimental AAA through upregulation of NF&kgr;B and ets. Inhibition of NF&kgr;B and ets could be a novel therapeutic strategy to treat AAA in hypertensive patients.

Improvement of survival of skin flaps by combined gene transfer of hepatocyte growth factor and prostacyclin synthase

Increasing the local blood flow is a critical factor for long‐term survival of skin flaps. Thus, a molecular therapy to increase the blood flow by means of an angiogenic factor is considered to be a useful strategy to improve skin flap survival. We focused on a combined strategy to stimulate not only angiogenesis, but also vasodilation of local microvessels, using co‐transfection of the hepatocyte growth factor (HGF) and prostacyclin synthase (PGIS) genes to enhance the survival of random‐pattern skin flaps.

Pulmonary artery dissection caused by extension of acute type B aortic dissection through the ductus arteriosus

Retrograde dissection from a type B aortic dissection usually involves the transverse arch and its branches and may also involve the ascending aorta following thoracic endovascular aortic repair. We present images of an acute dissection of the pulmonary artery (PA) caused by retrograde extension of an acute type B aortic dissection through a closed ductus arteriosus (DA). A 76-year-old hypertensive male presented with the sudden onset of back pain and dyspnea. A contrast-enhanced computed tomogram (CT) revealed an acute type B descending aortic dissection which extended retrograde across the thrombosed lumen of a closed DA with the dissection flap extending into the main PA (Figure 1A-C). The patient was treated medically with anti-hypertensive agents and analgesics. His condition stabilized and a follow-up CT scan 6 months later showed a completely thrombosed false lumen of both the descending aorta and PA (Figure 2A-C).

A Case of Ischemic Cardiomyopathy with Refractory Lethal Arrhythmia Which Successfully Underwent the Implantation of Left Ventricular Assist Device

Association of Takotsubo cardiomyopathy (TC) and complete atrioventricular block(CAVB) is rare. We present interesting two cases of TC with CAVB having different clinical courses. A 75-year-old women presented with dyspnea. On admission, she developed CAVB with junctional escape rhythm on electrocardiogram (ECG) and acute heart failure. After the treatment with temporary pacing, she underwent coronary angiography and left ventriculography which showed apical akinesis with normal coronary arteries. Her ECG improved to normal sinus rhythm without AV conduction disturbance for a week. Echocardiography showed complete recovery of apical wall motion within one month. The 123 I-metaiodobenzylguanidine imaging (MIBG) presented reduction of uptake in the apical area after the improvement of apical wall motion. She had fairly good clinical course with standard therapy for heart failure and discharged without pacemaker implantation on the 14th day. The second case was a 56-year-old women admitted for syncope. On admission, she also presented CAVB with junctional escape rhythm on ECG and akinesis of the apical area in echocardiography. Her coronary artery was normal and apical wall motion improved gradually. The 123Ismethyliodophenylpentadecanoic (BMIPP) acid imaging also showed the reduction of fatty acid metabolism in apical myocardium. She had been managed under temporary pacing for a week and was implanted permanent pacemaker without the recovery of AV conduction.