FBN1 and TGF? 1: Molecular mechanisms in the pathogenesis of thoracic aortic aneurysms and dissections

Thoracic aortic aneurysms (TAAD) develop asymptomatically until occurs aortic rupture or dissection often cause of morbidity. A high mortality is determined by TAAD and complications developing. 15,000 people die every year due to the complications of TAAD in USA. It takes 14th place according to the reasons of mortality among 55 years people and older.

The main risk factors for TAAD formation still remain under discussion. Hypertension, atherosclerosis, age, gender and eventually genetic predisposition are on the focus for the research. Only in certain cases it is caused by aortitis, atherosclerosis or inherited as a single gene mutation: in the fibrillin genes - Marfan syndrome, by inherited collagen mutations as in Ehler-Danlos syndrome, by mutations of the transforming growth factor-beta gene causing Loeys-Dietz syndrome or by actin gene mutations. Evidence has shown that FBN1 mutations may predispose TAA in the absence of phenotypic characteristics of Marfan syndrome. 

RNA silencing of lactate dehydrogenase gene in Rhizopus oryzae

Rhizopus oryzae is a filamentous fungus, belonging to the order Mucorales. It can ferment a wide range of carbohydrates hydrolyzed from lignocellulosic materials and even cellobiose to produce ethanol. However, R.oryzae also produces lactic acid as a major metabolite, which reduces the yield of ethanol. In this study, we show that significant reduction of lactic acid production could be achieved by short (25nt) synthetic siRNAs targeting the ldhA gene.

The average yield of lactic acid production by R. oryzae during the batch fermentation process, where glucose had been used as a sole carbon source, diminished from 0.07gm/gm in wild type to 0.01gm/gm in silenced samples. In contrast, the average yield of ethanol production increased from 0.39gm/gm in wild type to 0.45gm/gm in silenced samples. These results show 85.7% (gm/gm) reduction in lactic acid production as compared with the wild type R. oryzae, while an increase of 15.4% (gm/gm) in ethanol yield.