1,721,121 research outputs found
New diagnostic tools for left ventricular hypertrophy: biomolecular and echocardiographic techniques
No full textBackground: Left ventricular hypertrophy (LVH) is related to different physiological
and pathological conditions, as athlete's heart, systemic arterial hypertension, aortic
stenosis and hypertrophic cardiomyopathy. The secondary cardiac structural and
hemodynamic changes, referred as the “obesity cardiomyopathy” when these
alterations result in congestive heart failure, comprise an increase in left ventricular
wall thickness, mass and diameters, with systolic and diastolic dysfunction. MicroRNAs are small non-coding RNAs that regulate gene expression by inhibiting RNA translation. In myocardial tissue, microRNAs are involved in modulating phenomena such as cardiomyocyte (CM) hypertrophy, excitation-contraction coupling, and apoptosis; moreover, non-CM-specific microRNAs regulate myocardial vascularization and fibrosis. Recently, the possibility that circulating microRNAs may be biomarkers of cardiovascular disease has been raised, but studies are lacking.
Objective: We aimed to evaluate LVH by molecular and imaging techniques. LVH
was assessed in morbid obese patients, before and after sleeve gastrectomy by 2D
Doppler and TDI echocardiography (TTE), included speckle tracking imaging.
Moreover, we aimed to determine whether microRNAs involved in myocardial
remodeling were increased in the peripheral blood of patients with hypertrophic
cardiomyopathy (HCM); and if any significantly increased microRNA correlated with
the degree of left ventricular hypertrophy evaluated by TTE and cardiac magnetic
resonance.
Methods: Sixteen obese patients (46.4±10.3y, 4 males) underwent a complete cardiac evaluation including color Doppler/TDI TTE preoperatively and 16 months (range 12-18) after bariatric surgery. Fifty-six HCM patients were characterized with conventional TTE and cardiac magnetic resonance. MicroRNA expression was measured in peripheral plasma by reverse transcription and amplification of extracted RNA. The levels of circulating microRNA were compared with those in a control group made up of thirty-one blood donors.
Results: Echocardiographic data showed a significant reduction in interventricular septum, posterior wall thickness (from 11.3±1.8 to 9.4±2.1mm, from 10.4±1.7 to 8.6±1.9mm, respectively, p<0.01 both) and in left ventricular mass, absolute value and indexed by height (from 222.41±78.2 to 172.75±66.3g, p<0.05, from 55.9±14.3 to 43.8±17.2g/m2.7, p<0.001 both). Antihypertensive drugs intake was significantly reduced (p<0.05), such as the 10-year Framingham risk score (from 14.2±9.3% to 8.3±9.5%, p=0.003). Among those assessed, 12 microRNAs (miR-27, miR-199-5p, miR-26, miR-145, miR-133a, miR-143, miR-199-3p, miR-126-3p, miR-29, miR-155, miR-30, and miR-21) were significantly increased in the plasma of HCM patients. However, only miR-199-5p, miR-27, and miR-29 correlated with hypertrophy.
Conclusions: Our data suggest that LVH is significantly ameliorated after bariatric surgery, with a global cardiovascular risk reduction as demonstrated by the 10-year Framingham risk score. Moreover, cardiac remodeling determines a massive release of
microRNAs into the bloodstream of HCM patients
MicroRNAs in coronary heart disease. Ready to enter the clinical arena?
Full text linkCoronary artery disease (CAD) and its complication remain the leading cause of mortality in industrialized countries despite great advances in terms of diagnosis, prognosis, and treatment options. MicroRNAs (miRNAs), small noncoding RNAs, act as posttranscriptional gene expression modulators and have been implicated as key regulators in several physiological and pathological processes linked to CAD. Circulating miRNAs have been evaluated as promising novel biomarkers of CAD, acute coronary syndromes, and acute myocardial infarction, with prognostic implications. Several challenges related to technical aspects, miRNAs normalization, drugs interaction, and quality reporting of statistical multivariable analysis of the miRNAs observational studies remain unresolved. MicroRNA-based therapies in cardiovascular diseases are not ready yet for human trials but definitely appealing. Through this review we will provide clinicians with a concise overview of the pros and cons of microRNAs
MiR-21 and cardiac fibrosis. Another brick in the wall?
No full textOrgan fibrosis is a common final pathway of long-lasting and iterative tissue fibrosis, and is present in several pathologies, including ischaemic heart disease, diabetes mellitus, hypertension, and chronic kidney disease. Thus, it represents a widespread cause of morbidity and mortality. Tissue fibrosis is characterized by an excessive and uncontrolled deposition of extracellular matrix (ECM) elements. The development of fibrosis requires: (i) increased synthesis by matrix metalloproteinases (MMPs) and decreased degradation of ECM due to down-regulation of MMP inhibitors; (ii) the stimulation of profibrotic mediators, such as transforming growth factor-β (TGF-β), α-smooth muscle actin (α-SMA), platelet-derived growth factor (PDGF), and cytokines; (iii) the differentiation of fibroblasts into myofibroblasts, which express features of smooth muscle differentiation; and (iv) the recruitment of cells of an endothelial origin for endothelial to mesenchymal transition (EndMT), generating cells that still express endothelial markers while gaining fibroblast-like characteristics. In addition, innate and adaptive immune responses play an important role in development of fibrosis. Despite recent advances in the understanding of the mechanisms underlying its development, therapeutic strategies specifically aimed at fibrosis remain limited
Sacubitril/valsartan, left ventricular reverse remodeling and advanced echocardiographic imaging: is it a resolved conundrum?
No full textIn this issue of Minerva Cardiology and Angiology, Öz et al.1 reported the effects of sacubitril/ valsartan on short-term left ventricular (LV ) reverse remodeling evaluated by 2D and 3D echocardiography and 3D strain analysis. In this prospective cohort study, the positive effects of sacubitril/valsartan were evaluated in two different populations of heart failure (HF) with reduced ejection fraction (HFrEF): ischemic vs nonischemic patients. The authors applied advanced multiparametric 2D and 3D echocardiographic parameters to detect short-term minimal changes in LV diameters, volumes, LVE F and myocardial
strain parameters. This study was performed in a large dataset of 100 consecutive HFrEF patients eligible for treatment with sacubitril/valsartan, by 2D and, for the first time, 3D strain analysis
Morphological and chemical study of pathological deposits in human aortic and mitral valve stenosis. A biomineralogical contribution
Full text linkAim of this study was to investigate heart valve calcification process by different biomineralogical techniques to provide morphological and chemical features of the ectopic deposit extracted from patients with severe mitral and aortic valve stenosis, to better evaluate this pathological process. Polarized light microscopy and scanning electron microscopy analyses brought to light the presence of nodular and massive mineralization forms characterized by different levels of calcification, as well as the presence of submicrometric calcified globular cluster, micrometric cavities containing disorganized tissue structures, and submillimeter pockets formed by organic fibers very similar to amyloid formations. Electron microprobe analyses showed variable concentrations of Ca and P within each deposit and the highest content of Ca and P within calcified tricuspid aortic valves, while powder X-ray diffraction analyses indicated in the nanometer range the dimension of the pathological bioapati
Biominerals: nano-scale characterization of calcium phosphate crystals forming the “calcification” of the human heart valves
No full textCalcium phosphates, mainly ‘bioapatite’, make up the inorganic part of bone and teeth but also occur as pathological deposits. Among pathological biomineralizations, better known in the medical field with the generic term calcification, the deposition of calcium phosphate nanocrystals in the valve tissues of the human heart is a worldwide important topic associated with major morbidity, mortality and health economic costs. Nowadays the mechanisms leading to these pathological products are an open question despite all effort devoted to their comprehension. The nanometer scale structure of such pathological crystals was investigated using a dual beam Zeiss Auriga 405 HR-FESEM with resolution of 1 nm, and low accelerating voltage (< 15 kV) to obtain information about biomineral/organic structure interface. TEM analyses were performed on powdered samples by a Jeol JEM 2010 operating at 200KV with LaB6 source, nominal point resolution of 1.9 Å, and spherical aberration of 0.5 mm. Ultrastructural investigations brought to light the lowest units constituting the pathological deposits of the human valve tissues. These are represented by needle- and rod-like nanocrystals having the typical structure of hexagonal hydroxylapatite, but different chemical composition as [CO3]2- is present both for [PO4]3- and (OH)-. Characteristic aggregation properties of ‘bioapatite’ result in the formation of micrometer sized spherical particles. These latter appear to be also associated to mixed aggregates formed by nanocrystals and organic matrix, and to individual organic structures but without any relation to nanobacteria. All nanocrystals show the typical features of hydroxylapatite crystals precipitated in aqueous solutions, and a wide range of crystallite size, from a few to several hundreds of nanometers, that appears to be associated to local growth conditions and to different mineralization sites. The presence of localized compartments within the organic tissue, similar to “vugs” in rocks, in which a locally and progressive increase of ions concentration can take place, seems to be the pivotal requirement for the bioapatite precipitation. This confirms the important role of purely physicochemical processes in the biomineralization process of the valve tissues of the human heart and allows to ascribe to the organic matrix only the function of spatial template. However the presence of nanocrystals directly formed onto the organic substrate and oriented respect to this latter, also suggests a surface-induced mineralization process and a possible involvement of matrix components inducing ‘bioapatite’ nucleation
Pathological biomineralization from human aortic and mitral valve stenosis.
No full textSamples were collected as surgical waste from patients undergoing valvular replacement because of severe aortic (n=6) and mitral (n=2) stenosis. Pathological mineral formations have been investigated with XRPD and SEM-EDS, both in high and in low vacuum conditions. Samples were not coated because of metallic coating artifacts.The a cell parameters were found to be smaller than the a parameter of human dental enamel apatite, while the c parameters were greater. High resolution images show a complex relationship between inorganic component and organic matrix as well as particular morphologies of the pathogenic biomineralization. Bioapatite appears as lamellar crystals, globular aggregated and massive; at high magnification it appears to be constituted of spherical particles of variable size. Bioapatite morphology observed in this study appears to be different from biogenic calcium phosphate crystals and from inorganically produced counterparts. The small spheres could be considered as nanobacterial-like structures (?). This attractive hypothesis has not been confirmed yet
Calcification of the human heart valves: a mineralogical approach
No full textNormal physiologic processes result in development of mineralized tissue. Bones and tooth enamel are the main example of biominerals. Pathologic processes lead to calcification of the atherosclerotic plaques, kidney and salivary stones and other pathologic deposits. Most of these seem to be constituted from a mixture of calcium phosphate phases but their formation mechanisms are not completely known. In cardiac pathology, calcification of heart valves can be advanced by a congenital malformation or an infectious process or related to the senile degeneration. Pathological mineral deposits occurring in human cardiac valves were studied using Polarizing Microscopy, Scanning Electron Microscopy (SEM-EDS), Electron Microprobe (EMPA), X-Ray Powders Diffraction (XRPD), Infrared Spectroscopy (FTIR). Samples were obtained as surgical waste from thirty patients undergoing valvular replacement in case of severe aortic and mitral stenoses. The experimental results showed that the mineral phase grown in human cardiac valves is a calcium phosphate with poor crystallinity. It develops as nodules in the organic matrix. The FT-IR spectra may be used to infer the presence of carbonate group. The carbonate bands in the infrared spectra have a saw-tooth profile similar to sample PC18, a synthetic type A-B CAp but in samples of aortic valves a-parameter is smaller and the c-parameter is greater than those of PC18 [i.e. TV12 a=9.4165(8) Å, c= 6.8951(7) Å; PC18 a=9.4803(3) Å, c=6.8853(3) Å] probably due to substitutional carbonate groups in phosphate positions which cause a shrinkage in the a-parameter. Pathological phase investigated can be considered a bioapatite as the inorganic component of bone and tooth enamel, even if it possesses unusual morphologies for a calcium phosphate and a Ca/P ratio unlike that of normal mineralized tissue
Transprosthetic doppler gradients after aortic valve replacement with homograft: an echocardiographic follow-up study.
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