Normal Valves: Development and StructureNormal human semilunar valve development. Ninetyone semilunar valves from fetuses, neonates, children, and adults were studied (1). Valvular endothelial cells express an activated phenotype throughout gestation. Valvular interstitial cell density, proliferation, and apoptosis are higher in fetal than adult valves indicating matrix remodeling whereas in adults it is a quiescent fibroblast-like phenotype (Fig. 1). Elastin significantly increases postnatally (Fig. 2). The authors concluded: "Fetal valves possess a dynamic/adaptive structure and contain cells with an activated/immature phenotype. During postnatal life, activated cells gradually become quiescent, whereas collagen matures."
Familial Aggregation of Calcific Aortic Stenosis (AS)The geographic distribution of 2,527 operated patients with calcific AS was heterogeneous in areas in France, with frequencies of 1.13 to 9.38 of 1,000 inhabitants in different parishes (Fig. 3). From parishes with the highest rate of operated AS, there were 5 families in whom Ն3 siblings were affected. Genealogical examination traced a common ancestor within 13 generations in one of the families in whom 48 patients were derived from 34 nuclear families (2). Comment. These findings suggest a genetic component to calcific AS in some patients. An earlier study had shown the familial relative risk of death per year in those aged Ͻ65 years was 4 times higher in first degree relatives of those with aortic valve (AV) disease documenting a heritable component (3).
Mechanisms of Valvular Heart Disease (VHD)Low-density lipoprotein receptor-related protein (Lrp5). Low-density lipoprotein receptor-related protein, osteocalcin, and other osteochondrogenic differentiation markers are increased in calcified AV by protein and gene expression (p Ͻ 0.001) (4). Sox9, Lrp5 receptor, and osteocalcin were increased in myxomatous mitral valves (MV) by protein and gene expression (p Ͻ 0.001). Microcomputed tomography was positive in the calcified AV and negative in the myxomatous MV (Figs. 4 and 5). The authors concluded: "The mechanisms of VHD involve an endochondral bone process that is expressed as cartilage in MV and bone in AV. Up-regulation of the Lrp5 pathway may play a role." Human atrial ion channel and transporter subunit gene expression. Messenger ribonucleic acid expression was quantified in atrial tissues from 7 sinus rhythm-VHD, 11 atrial fibrillation (AF-VHD), and 11 control subjects (5). Principal findings were: VHD produces important changes in cardiac ion-channel gene expression, discrete ion-channel subunit changes differentiate patients with VHD who develop persistent AF from those who do not. Extravalvular cells in "degenerative" valves. Studies of AS and bioprosthetic valves showed that endothelial progenitor cells, dendritic cells, T-lymphocytes, and macrophages were much higher in bioprosthetic than in AS (6) ( Table 1). Comment. These findings suggest pathogenetic factors involved in degenerative native and bioprosthetic AS are probably di...