Possible extracardiac predictors of aortic dissection in Marfan syndrome.

BACKGROUND: According to previous studies, aortic diameter alone seems to be insufficient to predict the event of aortic dissection in Marfan syndrome (MFS). Determining the optimal schedule for preventive aortic root replacement (ARR) aortic growth rate is of importance, as well as family history, however, none of them appear to be decisive. Thus, the aim of this study was to search for potential predictors of aortic dissection in MFS. METHODS: A Marfan Biobank consisting of 79 MFS patients was established. Thirty-nine MFS patients who underwent ARR were assigned into three groups based on the indication for surgery (dissection, annuloaortic ectasia and prophylactic surgery). The prophylactic surgery group was excluded from the study. Transforming growth factor-ß (TGF-ß) serum levels were measured by ELISA, relative expression of c-Fos, matrix metalloproteinase 3 and 9 (MMP-3 and -9) were assessed by RT-PCR. Clinical parameters, including anthropometric variables - based on the original Ghent criteria were also analyzed. RESULTS: Among patients with aortic dissection, TGF-ß serum level was elevated (43.78 ± 6.51 vs. 31.64 ± 4.99 ng/l, p < 0.0001), MMP-3 was up-regulated (Ln2α = 1.87, p = 0.062) and striae atrophicae were more common (92% vs. 41% p = 0.027) compared to the annuloaortic ectasia group. CONCLUSIONS: We found three easily measurable parameters (striae atrophicae, TGF-ß serum level, MMP-3) that may help to predict the risk of aortic dissection in MFS. Based on these findings a new classification of MFS, that is benign or malignant is also proposed, which could be taken into consideration in determining the timing of prophylactic ARR.

The role of transforming growth factor-beta in Marfan syndrome.

The starting point, in Marfan syndrome (MFS) appears to be the mutation of fibrillin-1 gene whose deconstructed protein product cannot bind transforming growth factor beta (TGF-b), leading to an increased TGF-b tissue level. The aim of this review is to review the already known features of the cellular signal transduction downstream to TGF-b and its impact on the tissue homeostasis of microfibrils, and elastic fibers. We also investigate current data on the extracellular regulation of TGF-b level including mechanotransduction and the feedback cycles of integrin-dependent and independent activation of the latent TGF-b complex. Together these factors, by the destruction of the connective tissue fibers, may play an important role in the development of the diverse cardiac and extracardiac manifestations of MFS and many of them could be a target of conservative treatment. We present currently investigated drugs for the treatment of the syndrome, and explore possible avenues of research into pathogenesis of MFS in order to improve understanding of the disease.

Evidence of nitric oxide produced by the internal mammary artery graft in venous drainage of the recipient coronary artery.

BACKGROUND: The endothelium of the internal mammary artery produces nitric oxide in greater quantity than other vessels employed in revascularization of the ischemic myocardium. The aim of this study was to measure the concentration of stable metabolite (nitrite) of the endothelium-derived nitric oxide in the venous drainage (anterior interventricular vein) of the recipient coronary artery, which was the left anterior descending branch. The sampling was carried out before and after anastomosis completion. METHODS: Nitrite levels in the anterior interventricular vein, before and after anastomosis completion, in the left internal mammary artery free flow, and in the subclavian vein were measured. Fluroscopy after 4-hydroxycoumarin nitrozation was utilized to measure nitrite content of blood samples in 50 consecutive, partly heparinized patients undergoing off-pump coronary bypass surgery. Nitrate content of all samples was removed by Cadmium pearls. RESULTS: One hundred and sixty-four samples taken from 41 patients were feasable to analyze. A significant increase of nitric oxide (nitrite) level was found in the anterior interventricular vein, when comparing concentrations measured before and after the anastomosis between the left internal mammary artery and the left anterior descending artery. Mean values in the anterior inteventricular vein before and after anastomosis completion were as follows: 44.8 microMol (SD 4.9) and 70.7 microMol (SD 8.1), respectively. CONCLUSIONS: The increased production of nitric oxide by the internal mammary arterial graft may provide a perpetual vasodilatory response and partially protect the distal coronary vessel from atherosclerosis.

[Analysis of the stable metabolite of endothelium-derived nitric oxide of internal mammary artery bypass grafts at the venous drainage system of the recipient coronary artery. Morphologic implications and consequences]. / Az arteria mammaria interna bypass graft endotheliuma által termelt nitrogén-monoxid stabil metabolitjának mérése a recipiens coronariaág gyújtóeres rendszerében. Morfológiai vonatkozások és következmények.

INTRODUCTION: The internal mammary artery's endothelium continuously produces nitric oxide in a large quantity resulting in local and downstream vasodilatation, inhibition of platelet aggregation and in the tunica media prevents smooth muscle cell proliferation. OBJECTIVE: The aim of this study was to measure the concentration of the internal mammary artery bypass graft's endothelium derived nitric oxide's stable metabolite, (nitrite) at the venous drainage site (great cardiac vein) of the recipient coronary artery (left anterior descending), and to prove that the change of the biochemical milieu provides morphological stability (vasodilation and lack of atherosclerosis) in the recipient coronary artery based on recoronarographies. METHOD: Authors investigated the levels of endothelium derived nitric oxide in intraoperative settings of 50 off pump, partly heparinized coronary bypass surgery cases sampling from the internal mammary free cut end flow (81.2 +/- 12.1 mumol/l), the great cardiac vein (anterior interventricular vein) prior and after arterial bypass graft completion and in the systemic circulation (42.9 +/- 7.1 mumol/l), The stable metabolite concentration measurement was carried out with the modified Takafumi Ohta method utilizing fluoroscopy. Out of the 200 samples 164 were feasible to analyze. RESULTS: A significant increase was found in the great cardiac vein, comparing concentrations measured prior and after IMA anastomosis completion: 46.7 +/- 11.4 mumol/l, and 71.12 +/- 13.1 mumol/l, respectively (p < 0.05). CONCLUSION: Based on these findings, due to the continuous protective (vasodilatative and antiatherogen) effect of the IMA provided EDNO, the recipient artery shows no pathological changes in time. This was proved by studying recoronarographies of 103 patients--with prior coronary bypass surgery in 5-12 years using the IMA, and with new symptomatology. Out of 87 functioning IMA to LAD grafts, 85 LAD showed no atherosclerotic changes, while in the same patients' other coronary systems significant, de novo stenotic lesions had developed.