The findings suggest an association between obesity and the 825T allele, a genetic marker for enhanced G protein reactivity, in hypertensive individuals.

In young patients with mild hypertension without heart disease the 825T allele is associated with an increased left ventricular mass index. These hypothesis-generating data suggest that GNB3 825T allele may be considered as one genetic marker predisposing to an increase in left ventricular mass in hypertensives, and justifies larger studies.

Debris was captured in 99% of patients, of whom 53% had at least 1 particle of debris >1 mm. The number and size of particles captured during a procedure in which EvR or Lotus THV was used were higher and larger than with a Sapien THV. Regardless, embolic debris, including large particles, is universal across valve types and provides mechanistic support for the potential benefit of using cerebral embolic protection in all TAVR procedures.

Monocyte apoptosis is an important determinant of atherothrombosis. Two major mechanisms for apoptosis-associated thrombogenicity have been described: exposure of negatively charged membrane phospholipids and up-regulation of tissue factor (TF). However, the relative importance of these mechanisms is unclear. Thus, procoagulant functions (thrombin generation) of apoptotic (staurosporine, 2 muM, 24 h) U937 cells versus cell-derived microparticles (MPs) were studied. In apoptotic U937 cells, a significant increase in TF mRNA (real-time PCR), surface expression of TF (flow cytometry), and total cellular amount of TF (Western blotting) was observed. Control cells only minimally triggered thrombin generation (endogenous thrombin potential), and apoptotic cells were highly procoagulant. However, addition of negatively charged membranes completely restored the thrombin generation capacity of control U937 cells to the levels of apoptotic cells. MPs (defined as CD45(+) particles of subcellular size), derived from apoptotic U937 cells, were highly procoagulant but did not exhibit an increased TF expression or annexin V binding. Taken together, our data support the concept that the membrane environment, independent of TF expression, determines the extent of thrombin formation triggered by apoptosis of monocytic cells. Externalization of negatively charged phospholipids represents the most important mechanisms for whole cells. Additional yet unknown mechanisms appear to be involved in the procoagulant actions of MPs derived from apoptotic monocytes.

Our findings suggest a pathophysiologically relevant role for the T-786C polymorphism in human coronary vasomotion. The observed linkage disequilibrium between both NOS3 genotypes deserves further research in future studies.