Abstract-Integrins link the extracellular matrix to the cellular cytoskeleton and serve important roles in cell growth, differentiation, migration, and survival. Ablation of 1 integrin in all murine tissues results in peri-implantation embryonic lethality. To investigate the role of 1 integrin in the myocardium, we used Cre-LoxP technology to inactivate the 1 integrin gene exclusively in ventricular cardiac myocytes. Animals with homozygous ventricular myocyte 1 integrin gene excision were born in appropriate numbers and grew into adulthood. These animals had 18% of control levels of 1D integrin protein in the heart and displayed myocardial fibrosis. High-fidelity micromanometer-tipped catheterization of the intact 5-week-old 1 integrin knockout mice showed depressed left ventricular basal and dobutamine-stimulated contractility and relaxation (LV dP/dt max and LV dP/dt min ) as compared with control groups (nϭ8 to 10 of each, PϽ0.01). Hemodynamic loading imposed by 7 days of transverse aortic constriction showed that the 1 integrin knockout mice were intolerant of this stress as they had 53% survival versus 88% in controls (nϭ15 each). Key Words: extracellular matrix Ⅲ homologous recombination Ⅲ Cre recombinase Ⅲ heart Ⅲ positron emission tomography I ntegrins are a large family of heterodimeric cell surface receptors composed of ␣ and  subunits. They function in cell-extracellular matrix (ECM) adhesion and cell-cell adhesion, and signal bidirectionally across the cell membrane. 1,2 Further, they serve as mechanotransducers, converting mechanical signals to biochemical ones. 3 This combination of properties allows integrins to play important roles in cell growth, differentiation, migration, and survival 4 and also makes them attractive candidates for essential roles in the developing and postnatal heart.Our previous work has shown that 1 integrins are linked to the hypertrophic response of cultured ventricular myocytes and also that dominant-negative disruption of integrin function in transgenic mice resulted in cardiac fibrosis and abnormal cardiac function. 5-7 Ablation of 1 integrin expression in all murine tissues resulted in gastrulation defects and death by E5.5 of the 21-day gestation period. 8,9 Chimeric mice as well as embryoid bodies constructed from 1 integrin-null cells showed delayed development and differentiation of 1-deficient cells along the cardiac lineage, as well as abnormal sarcomerogenesis of these cardiac-like cells. 10 Although a few 1 integrin-null cells were detected in the myocardium of chimeric mice, cellular debris was always detected along with the null cells. These null cells were completely lost from the myocardium of the chimeric mouse heart by 6 months of age.To more specifically evaluate the role of 1 integrin in the myocardium, we used a Cre-loxP gene targeting approach. Cre recombinase expression driven by the myosin light chain-2 ventricular (MLC-2v) promoter caused 1 integrin gene excision exclusively in ventricular cardiac myocytes. 11 Our results in these ...
Except for the recurrent artery of Heubner and the anterior choroidal artery, MDCT angiography depicted 90% or more of all examined small intracranial arteries detected with digital subtraction angiography. The mean sensitivity was 0.91, and the mean specificity was 0.7.
Our analysis shows that a critical shortage of endovascular trained specialists will exist in the future. More surgeons need to receive endovascular training to meet these future needs.
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