Functional consequences of an LMNA mutation associated with a new cardiac and non-cardiac phenotype.

Heritable dilated cardiomyopathy is a genetically highly heterogeneous disease. To date 17 different chromosomal loci have been described for autosomal dominant forms of dilated cardiomyopathy with or without additional clinical manifestations. Among the 10 mutated genes associated with dilated cardiomyopathy, the lamin A/C (LMNA) gene has been reported in forms associated with conduction-system disease with or without skeletal muscle myopathy.

A new locus for autosomal dominant dilated cardiomyopathy identified on chromosome 6q12-q16.

Dilated cardiomyopathy (DCM) is a heart-muscle disease characterized by ventricular dilatation and impaired heart contraction and is heterogeneous both clinically and genetically. To date, 12 candidate disease loci have been described for autosomal dominant DCM. We report the identification of a new locus on chromosome 6q12-16 in a French family with 9 individuals affected by the pure form of autosomal dominant DCM.

Epidemiology of desmin and cardiac actin gene mutations in a european population of dilated cardiomyopathy.

Aims: Although dilated cardiomyopathy is the most frequent form of cardiomyopathy, its aetiology is still poorly understood. In about 20-30% of cases the disease is familial with a large predominance of autosomal dominant transmission. Ten different chromosomal loci have been described for autosomal dominant forms of dilated cardiomyopathy.

Identification of a genetic risk factor for idiopathic dilated cardiomyopathy. Involvement of a polymorphism in the endothelin receptor type A gene. CARDIGENE group.

Background: Idiopathic dilated cardiomyopathy is a frequent cause of heart failure, a major concern of public health. Although idiopathic dilated cardiomyopathy may be familial, most cases are sporadic and the disease is considered to be multifactorial, for which genetic factors may account for a significant part.

Methods And Results: We hypothesized that genetic abnormalities of the endothelin pathway may be involved in idiopathic dilated cardiomyopathy pathophysiology and therefore examined the possible association between idiopathic dilated cardiomyopathy and polymorphisms in genes encoding endothelin 1, endothelin type A and type B receptors, in a case-control study (433 patients and 400 age- and sex-matched control subjects).

Characterization of a unique genetic variant in the beta1-adrenoceptor gene and evaluation of its role in idiopathic dilated cardiomyopathy. CARDIGENE Group.

The genetic factors that underlie idiopathic dilated cardiomyopathy (IDCM) have not yet been elucidated. Since beta1-adrenoceptors are downregulated in patients with IDCM, and since beta-blocker therapy is consistently beneficial in this setting, we hypothesized that genetic variation in the beta1-adrenoceptor might affect susceptibility to and/or severity of IDCM. As no intragenic polymorphism was available, a systematic screening of the gene was first performed.

Morphometric and metabolic profile of the distal segment of the internal mammary artery: caution on its use for coronary anastomoses.

Objective: Elastic arteries were found to be less prone to intimal hyperplasia than muscular arteries. The internal mammary artery (IMA), which is elastic in its proximal segment, presents a gradual decrease of media elastic fibers along its downstream course. Metabolic and morphometric studies of the distal end of the IMA with regard to its local susceptibility to develop intimal changes were undertaken in order to evaluate the reliability of its use as an anastomotic site for bypass grafting.

Effect of cold anoxia and cryopreservation on metabolic and contractile functions of human mammary artery.

The ability of human internal mammary artery smooth muscle cells to maintain histoenzymatic activity and contractile response after various times of cold anoxia prior to and following cryostorage was evaluated. The results showed that the enzyme histochemical status of human mammary arteries was largely unchanged after both cold anoxia and cryopreservation. Neither in fresh nor in cryopreserved mammary arteries did cold anoxia for up to 24 h change maximal contractile responses to potassium depolarization and norepinephrine.

Viability of cryopreserved arterial wall: enzyme-histochemical and physiological markers.

Use of cryopreserved small-caliber arterial allografts for arterial bypass procedures has been suggested. In addition to immunological tolerance, long term in vivo success of these grafts may be dependent on the viability of arterial cells after cryopreservation. Metabolic and functional capabilities of arterial smooth muscle cells were evaluated by studying the enzyme histochemical expressions of sheep carotid arteries after various time of cryopreservation (7 days, 90 to 150 days) and their contractile responses after freezing.

[Experimental immune arteriosclerosis in the rabbit. Immunogenic and pathogenic properties of glycoproteins and elastins in arterial tissue].

Rabbits immunized with kappa elastin produced arteriosclerosis and antibodies that bound to target-structures (elastic fiber sheaths, endothelial and smooth muscle cells). These antibodies were cytotoxic for cultured rabbit or rat arterial smooth muscle cells. Absorption of the antielastin antiserum with pig aorta or human serum glycoproteins inhibited its binding to target-structures and suppressed its in vitro cytotoxicity.

In vitro immune aggression against rabbit aortic smooth muscle cells.

Rabbit aortic smooth muscle cells cultivated with certain antisera underwent growth changes and necrosis. These cytotoxic antisera were obtained by immunizing rabbits against rat aorta, human or pig aortic glycoproteins, human serum glycoproteins and E. coli lipopolysaccharide.