Lamin A/C Ablation Restricted to Vascular Smooth Muscle Cells, Cardiomyocytes, and Cardiac Fibroblasts Causes Cardiac and Vascular Dysfunction.

Mutations in the LMNA gene (encoding lamin A/C proteins) cause several human cardiac diseases, including dilated cardiomyopathies (LMNA-DCM). The main clinical risks in LMNA-DCM patients are sudden cardiac death and progressive left ventricular ejection fraction deterioration, and therefore most human and animal studies have sought to define the mechanisms through which LMNA mutations provoke cardiac alterations, with a particular focus on cardiomyocytes. To investigate if LMNA mutations also cause vascular alterations that might contribute to the etiopathogenesis of LMNA-DCM, we generated and characterized Lmnaflox/floxSM22αCre mice, which constitutively lack lamin A/C in vascular smooth muscle cells (VSMCs), cardiac fibroblasts, and cardiomyocytes. Like mice with whole body or cardiomyocyte-specific lamin A/C ablation, Lmnaflox/floxSM22αCre mice recapitulated the main hallmarks of human LMNA-DCM, including ventricular systolic dysfunction, cardiac conduction defects, cardiac fibrosis, and premature death. These alterations were associated with elevated expression of total and phosphorylated (active) Smad3 and cleaved (active) caspase 3 in the heart. Lmnaflox/floxSM22αCre mice also exhibited perivascular fibrosis in the coronary arteries and a switch of aortic VSMCs from the 'contractile' to the 'synthetic' phenotype. Ex vivo wire myography in isolated aortic rings revealed impaired maximum contraction capacity and an altered response to vasoconstrictor and vasodilator agents in Lmnaflox/floxSM22αCre mice. To our knowledge, our results provide the first evidence of phenotypic alterations in VSMCs that might contribute significantly to the pathophysiology of some forms of LMNA-DCM. Future work addressing the mechanisms underlying vascular defects in LMNA-DCM may open new therapeutic avenues for these diseases.

Examining the Effect of Ionizing Radiations in Ion-Exchange Membranes of Interest in Biomedical Applications.

The possible effects of ionizing radiation on four commercial membranes, which are typically used as electrolytes in fuel cells supplying energy to a huge variety of medical implantable devices, were studied. These devices could obtain energy from the biological environment through a glucose fuel cell, which could be a good candidate to replace conventional batteries as a power source. In these applications, materials with high radiation stability for the fuel cell elements would be disabled. The polymeric membrane is one of the key elements in fuel cells. Membrane swelling properties are very important because they affect the fuel cell's performance. For this reason, the swelling behaviors of various samples of each membrane irradiated with different doses were analyzed. Each sample was irradiated with a typical dose of a conventional radiotherapy treatment, and the regular conditions of the biological working environment were simulated. The target was to examine the possible effect of the received radiation on the membranes. The results show that the ionizing radiation influenced their swelling properties, as well as that dimensional changes were dependent on the existence of reinforcement, be it internal or external, in the membrane structure.