Search

BackgroundThe extent of myocardial fibrosis in patients with severe aortic stenosis might have an important prognostic value. Non-invasive imaging to quantify myocardial fibrosis by measuring extracellular volume fraction might have an important clinical utility prior to aortic valve intervention.MethodsSeventy-five consecutive patients with severe aortic stenosis, and 19 normal subjects were prospectively recruited and underwent pre- and post-contrast computed tomography for estimating myocardial extracellular volume fraction. Serum level of galectin-3 was measured and 2-dimensional echocardiography was performed to characterize the extent of cardiac damage using a recently published aortic stenosis staging classification.ResultsExtracellular volume fraction was higher in patients with aortic stenosis compared to normal subjects (40.0±11% vs. 21.6±5.6%; respectively, pConclusionIn patients with severe aortic stenosis undergoing computed tomography before aortic valve intervention, quantification of extracellular volume fraction correlated with functional status and markers of left ventricular decompensation, and predicted the 12-months composite adverse clinical outcomes. Implementation of this novel technique might aid in the risk stratification process before aortic valve interventions.

BackgroundGestational diabetes mellitus (GDM) is associated with future cardiovascular morbidity and recognized as a women-specific risk factor for cardiovascular disease. The mechanisms for this association are not well established. Therefore, we aimed to evaluate the cardiovascular-related biomarkers, galectin-3 (Gal-3) and protein convertase subtilisin/kexin (PCSK) type 9, in women with GDM.MethodsBlood samples were drawn in the third trimester from 31 women diagnosed with GDM and from 35 women with normal pregnancies. Blood levels of Gal-3 and PCSK-9 were measured using a quantitative sandwich enzyme immunoassay. In addition, we measured Gal-3 levels in 24 pregnant women in the first trimester who later developed GDM and in 36 healthy controls. Continuous variables were compared using student's t-test and categorical variables by chi-square/fisher's exact tests.ResultsWe found increased levels of Gal-3 in women diagnosed with GDM compared to women without GDM (124.6±32% versus control; pv = 0.001). Furthermore, we demonstrated elevated levels of Gal-3 during the first trimester among women who later developed GDM compared with women who did not develop any gestational morbidity (125.7±32% versus control; pv = 0.004). Third-trimester levels of PCSK-9 did not differ between women with and without GDM (560±45ng/mL versus 553±33ng/mL; pv = 0.4).ConclusionsThe results suggest a possible mechanism that may link GDM to the future increased cardiovascular risk in these patients. Additionally, increased Gal-3 levels during the first trimester may suggest a new early predictor for GDM.

BackgroundDecisions on dual antiplatelet therapy (DAPT) duration should balance the opposing risks of ischaemia and bleeding. Our aim was to develop a risk score to identify stable coronary artery disease (SCAD) patients undergoing PCI who would benefit or suffer from extending DAPT beyond 6 months.MethodsRetrospective analysis of a cohort of patients who completed 6 months of DAPT following PCI. Predictors of ischaemic and bleeding events for the 6-12 month period post-PCI were identified and a risk score was developed to estimate the likelihood of benefiting from extending DAPT beyond 6 months. Incidence of mortality, ischaemic and bleeding events for patients treated with DAPT for 6 vs. 6-12 months, was compared, stratified by strata of the risk score.ResultsThe study included 2,699 patients. Over 6 months' follow up, there were 78 (2.9%) ischaemic and 43 (1.6%) bleeding events. Four variables (heart failure, left ventricular ejection fraction ≤30%, left main or three vessel CAD, status post (s/p) PCI and s/p stroke) predicted ischemic events, two variables (age>75, haemoglobin ConclusionIn a population of SCAD patients who completed 6 months of DAPT, a risk score for subsequent ischaemic and bleeding events identified patients likely to benefit from continuing or stopping DAPT.

Endothelial progenitor cells (EPCs) are a population of bone marrow-derived cells, which have an important role in the process of endothelialization and vascular repair following injury. Impairment of EPCs, which occurs in patients with diabetes, was shown to be related to endothelial dysfunction, coronary artery disease (CAD) and adverse clinical outcomes. Recent evidence has shown that calcitriol, the active hormone of vitamin D, has a favorable impact on the endothelium and cardiovascular system. There is limited data on the effect of vitamin D on EPCs function.To examine the in vitro effects of Calcitriol on EPCs from healthy subjects and patients with diabetes.Fifty-one patients with type 2 diabetes (60±11 years, 40% women, HbA1C: 9.1±0.8%) and 23 healthy volunteers were recruited. EPCs were isolated and cultured with and without calcitriol. The capacity of the cells to form colony-forming units (CFUs), their viability (measured by MTT assay), KLF-10 levels and angiogenic markers were evaluated after 1 week of culture.In diabetic patients, EPC CFUs and cell viability were higher in EPCs exposed to calcitriol vs. EPCs not exposed to calcitriol [EPC CFUs: 1.25 (IQR 1.0-2.0) vs. 0.5 (IQR 0.5-1.9), p < 0.001; MTT:0.62 (IQR 0.44-0.93) vs. 0.52 (IQR 0.31-0.62), p = 0.001]. KLF-10 levels tended to be higher in EPCs exposed to vitamin D, with no differences in angiopoietic markers. In healthy subjects, calcitriol supplementation also resulted in higher cell viability [MTT: 0.23 (IQR 0.11-0.46) vs. 0.19 (0.09-0.39), p = 0.04], but without differences in CFU count or angiopoietic markers.In patients with diabetes mellitus, in vitro vitamin D supplementation improved EPCs capacity to form colonies and viability. Further studies regarding the mechanisms by which vitamin D exerts its effect are required.

Systemic growth and branching stimuli, and appropriate interactions with the host stroma are essential for the development of foreign epithelia in the mammary gland of immunodeficient mice. These factors were manipulated to promote and investigate the generation of representative bovine epithelial morphology in the transplanted mouse mammary stroma. The bovine mammary epithelium is unique in its commitment to rapid proliferation and high rate of differentiation. Its morphological organization within a fibrotic stroma resembles that of the human breast, and differs significantly from the rudimentary ductal network that penetrates a fatty stroma in mice. Transplantation of bovine mammary epithelial cells into the cleared mammary fat pad of NOD-SCID mice led to continuous growth of epithelial structures. Multilayered hollow spheres developed within fibrotic areas, but in contrast to mice, no epithelial organization was formed between adipocytes. The multilayered spheres shared characteristics with the heifer gland's epithelium, including lumen size, cell proliferation, cytokeratin orientation, estrogen/progesterone receptor expression and localization, and milk protein synthesis. However, they did not extend into the mouse fat pad via ductal morphology. Pre-transplantation of fibroblasts increased the number of spheres, but did not promote extension of bovine morphology. The bovine cells preserved their fate and rarely participated in chimeric mouse-bovine outgrowths. Nevertheless, a single case of terminal ductal lobuloalveolar unit (TDLU) development was recorded in mice treated with estrogen and progesterone, implying the feasibility of this representative bovine morphology's development. In vitro extension of these studies revealed paracrine inhibition of bovine epithelial mammosphere development by adipocytes, which was also generalized to breast epithelial mammosphere formation. The rescue of mammosphere development by fibroblast growth factor administration evidences an active equilibrium between inhibitory and supportive effects exerted by the adipose and fibrotic regions of the stroma, respectively, which determines the development of foreign epithelium.