The renin‐angiotensin‐aldosterone system and its suppression

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148403/1/jvim15454-sup-0001-supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148403/2/jvim15454-sup-0002-figures.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148403/3/jvim15454-sup-0005-TableS3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148403/4/jvim15454-sup-0004-TableS2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148403/5/jvim15454-sup-0007-TableS5.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148403/6/jvim15454_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148403/7/jvim15454.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148403/8/jvim15454-sup-0006-TableS4.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148403/9/jvim15454-sup-0003-TableS1.pd

Thrombospondins in the heart: potential functions in cardiac remodeling

Cardiac remodeling after myocardial injury involves inflammation, angiogenesis, left ventricular hypertrophy and matrix remodeling. Thrombospondins (TSPs) belong to the group of matricellular proteins, which are non-structural extracellular matrix proteins that modulate cell–matrix interactions and cell function in injured tissues or tumors. They interact with different matrix and membrane-bound proteins due to their diverse functional domains. That the expression of TSPs strongly increases during cardiac stress or injury indicates an important role for them during cardiac remodeling. Recently, the protective properties of TSP expression against heart failure have been acknowledged. The current review will focus on the biological role of TSPs in the ischemic and hypertensive heart, and will describe the functional consequences of TSP polymorphisms in cardiac disease

Non-uniform recovery of left ventricular transmural mechanics in ST-segment elevation myocardial infarction

<p>Abstract</p> <p>Background</p> <p>After a transient ischemic episode, the subendocardial region is more severely injured than outer subepicardial layers and may regain a proportionately greater degree of mechanical function in the longitudinal direction. We sought to explore left ventricular (LV) transmural mechanics in patients with ST-segment elevation myocardial infarction (STEMI) for determining the mechanism underlying recovery of global LV function after primary percutaneous coronary intervention (PCI).</p> <p>Methods</p> <p>A total of 42 patients (62 ± 11 years old, 71% male) with a first STEMI underwent serial assessments of LV longitudinal, circumferential and radial strains (LS, CS and RS) by selective tracking of subendocardial and subepicardial regions within 48 hours and a median of 5 months after PCI. LV mechanical parameters were compared with sixteen age and gender matched normal controls.</p> <p>Results</p> <p>In comparison with controls, endocardial and epicardial LS were markedly attenuated at 48 hours following PCI (P < 0.001). An improvement in LV ejection fraction (EF > 5%) following PCI was seen in 24 (57%) patients and was associated with improvement in endocardial and epicardial LS (P < 0.001 and P = 0.003, respectively) and endocardial CS (P = 0.01). Radial strain and wall motion score index, however, remained persistently abnormal. The change in endocardial LS (OR 1.2, 95% CI 1.03 to 1.42, P = 0.01) and the change in epicardial LS (OR 1.2, 95% 1.03 to 1.46, P = 0.02) were significantly associated with the improvement in LVEF, independent of the location of STEMI and the presence of underlying multivessel disease.</p> <p>Conclusions</p> <p>In patients with STEMI treated by PCI, the recovery of LV subendocardial shortening strain seen in the longitudinal direction underlies the improvement in LV global function despite persistent abnormalities in radial mechanics and wall motion score index.</p

Plasma Levels of Transforming Growth Factor-β1 Reflect Left Ventricular Remodeling in Aortic Stenosis

Background: TGF-b1 is involved in cardiac remodeling through an auto/paracrine mechanism. The contribution of TGF-b1 from plasmatic source to pressure overload myocardial remodeling has not been analyzed. We investigated, in patients with valvular aortic stenosis (AS), and in mice subjected to transverse aortic arch constriction (TAC), whether plasma TGF-b1 relates with myocardial remodeling, reflected by LV transcriptional adaptations of genes linked to myocardial hypertrophy and fibrosis, and by heart morphology and function. Methodology/Principal Findings: The subjects of the study were: 39 patients operated of AS; 27 healthy volunteers; 12 mice subjected to TAC; and 6 mice sham-operated. Myocardial samples were subjected to quantitative PCR. Plasma TGF-b1 was determined by ELISA. Under pressure overload, TGF-b1 plasma levels were significantly increased both in AS patients and TAC mice. In AS patients, plasma TGF-b1 correlated directly with aortic transvalvular gradients and LV mass surrogate variables, both preoperatively and 1 year after surgery. Plasma TGF-b1 correlated positively with the myocardial expression of genes encoding extracellular matrix (collagens I and III, fibronectin) and sarcomeric (myosin light chain-2, b-myosin heavy chain) remodelling targets of TGF-b1, in TAC mice and in AS patients. Conclusions/Significance: A circulating TGF-b1-mediated mechanism is involved, in both mice and humans, in the excessive deposition of ECM elements and hypertrophic growth of cardiomyocytes under pressure overload. The possible value of plasma TGF-b1 as a marker reflecting preoperative myocardial remodeling status in AS patients deserves further analysis in larger patient cohorts

Traffic-related air pollution and respiratory symptoms among asthmatic children, resident in Mexico City: the EVA cohort study

<p>Abstract</p> <p>Background</p> <p>Taffic-related air pollution has been related to adverse respiratory outcomes; however, there is still uncertainty concerning the type of vehicle emission causing most deleterious effects.</p> <p>Methods</p> <p>A panel study was conducted among 147 asthmatic and 50 healthy children, who were followed up for an average of 22 weeks. Incidence density of coughing, wheezing and breathing difficulty was assessed by referring to daily records of symptoms and child's medication. The association between exposure to pollutants and occurrence of symptoms was evaluated using mixed-effect models with binary response and poisson regression.</p> <p>Results</p> <p>Wheezing was found to relate significantly to air pollutants: an increase of 17.4 μg/m³(IQR) of PM_2.5(24-h average) was associated with an 8.8% increase (95% CI: 2.4% to 15.5%); an increase of 34 ppb (IQR) of NO₂(1-h maximum) was associated with an 9.1% increase (95% CI: 2.3% to16.4%) and an increase of 48 ppb (IQR) in O₃levels (1 hr maximum) to an increase of 10% (95% CI: 3.2% to 17.3%). Diesel-fueled motor vehicles were significantly associated with wheezing and bronchodilator use (IRR = 1.29; 95% CI: 1.03 to 1.62, and IRR = 1.32; 95% CI: 0.99 to 1.77, respectively, for an increase of 130 vehicles hourly, above the 24-hour average).</p> <p>Conclusion</p> <p>Respiratory symptoms in asthmatic children were significantly associated with exposure to traffic exhaust, especially from natural gas and diesel-fueled vehicles.</p

Long-term survival in patients with non-small cell lung cancer and synchronous brain metastasis treated with whole-brain radiotherapy and thoracic chemoradiation

<p>Abstract</p> <p>Background</p> <p>Brain metastases occur in 30-50% of Non-small cell lung cancer (NSCLC) patients and confer a worse prognosis and quality of life. These patients are usually treated with Whole-brain radiotherapy (WBRT) followed by systemic therapy. Few studies have evaluated the role of chemoradiotherapy to the primary tumor after WBRT as definitive treatment in the management of these patients.</p> <p>Methods</p> <p>We reviewed the outcome of 30 patients with primary NSCLC and brain metastasis at diagnosis without evidence of other metastatic sites. Patients were treated with WBRT and after induction chemotherapy with paclitaxel and cisplatin for two cycles. In the absence of progression, concurrent chemoradiotherapy for the primary tumor with weekly paclitaxel and carboplatin was indicated, with a total effective dose of 60 Gy. If disease progression was ruled out, four chemotherapy cycles followed.</p> <p>Results</p> <p>Median Progression-free survival (PFS) and Overall survival (OS) were 8.43 ± 1.5 and 31.8 ± 15.8 months, respectively. PFS was 39.5% at 1 year and 24.7% at 2 years. The 1- and 2-year OS rates were 71.1 and 60.2%, respectively. Three-year OS was significantly superior for patients with N0-N1 stage disease vs. N2-N3 (60 vs. 24%, respectively; Response rate [RR], 0.03; <it>p</it>= 0.038).</p> <p>Conclusions</p> <p>Patients with NSCLC and brain metastasis might benefit from treatment with WBRT and concurrent thoracic chemoradiotherapy. The subgroup of N0-N1 patients appears to achieve the greatest benefit. The result of this study warrants a prospective trial to confirm the benefit of this treatment.</p

Remodelling of the angular collagen fiber distribution in cardiovascular tissues

Understanding collagen fiber remodelling is desired to optimize the mechanical conditioning protocols in tissue-engineering of load-bearing cardiovascular structures. Mathematical models offer strong possibilities to gain insight into the mechanisms and mechanical stimuli involved in these remodelling processes. In this study, a framework is proposed to investigate remodelling of angular collagen fiber distribution in cardiovascular tissues. A structurally based model for collagenous cardiovascular tissues is extended with remodelling laws for the collagen architecture, and the model is subsequently applied to the arterial wall and aortic valve. For the arterial wall, the model predicts the presence of two helically arranged families of collagen fibers. A branching, diverging hammock-type fiber architecture is predicted for the aortic valve. It is expected that the proposed model may be of great potential for the design of improved tissue engineering protocols and may give further insight into the pathophysiology of cardiovascular diseases

Cardiomyocyte-specific inactivation of thyroid hormone in pathologic ventricular hypertrophy: an adaptative response or part of the problem?

Recent studies in various rodent models of pathologic ventricular hypertrophy report the re-expression of deiodinase type 3 (D3) in cardiomyocytes. D3 inactivates thyroid hormone (T3) and is mainly expressed in tissues during development. The stimulation of D3 activity in ventricular hypertrophy and subsequent heart failure is associated with severe impairment of cardiac T3 signaling. Hypoxia-induced signaling appears to drive D3 expression in the hypertrophic cardiomyocyte, but other signaling cascades implicated in hypertrophy are also capable of stimulating transcription of the DIO3 gene. Many cardiac genes are transcriptionally regulated by T3 and impairment of T3 signaling will not only reduce energy turnover, but also lead to changes in gene expression that contribute to contractile dysfunction in pathologic remodeling. Whether stimulation of D3 activity and the ensuing local T3-deficiency is an adaptive response of the stressed heart or part of the pathologic signaling network leading to heart failure, remains to be established

Contribution of Exogenous Genetic Elements to the Group A Streptococcus Metagenome

Variation in gene content among strains of a bacterial species contributes to biomedically relevant differences in phenotypes such as virulence and antimicrobial resistance. Group A Streptococcus (GAS) causes a diverse array of human infections and sequelae, and exhibits a complex pathogenic behavior. To enhance our understanding of genotype-phenotype relationships in this important pathogen, we determined the complete genome sequences of four GAS strains expressing M protein serotypes (M2, M4, and 2 M12) that commonly cause noninvasive and invasive infections. These sequences were compared with eight previously determined GAS genomes and regions of variably present gene content were assessed. Consistent with the previously determined genomes, each of the new genomes is ∼1.9 Mb in size, with ∼10% of the gene content of each encoded on variably present exogenous genetic elements. Like the other GAS genomes, these four genomes are polylysogenic and prophage encode the majority of the variably present gene content of each. In contrast to most of the previously determined genomes, multiple exogenous integrated conjugative elements (ICEs) with characteristics of conjugative transposons and plasmids are present in these new genomes. Cumulatively, 242 new GAS metagenome genes were identified that were not present in the previously sequenced genomes. Importantly, ICEs accounted for 41% of the new GAS metagenome gene content identified in these four genomes. Two large ICEs, designated 2096-RD.2 (63 kb) and 10750-RD.2 (49 kb), have multiple genes encoding resistance to antimicrobial agents, including tetracycline and erythromycin, respectively. Also resident on these ICEs are three genes encoding inferred extracellular proteins of unknown function, including a predicted cell surface protein that is only present in the genome of the serotype M12 strain cultured from a patient with acute poststreptococcal glomerulonephritis. The data provide new information about the GAS metagenome and will assist studies of pathogenesis, antimicrobial resistance, and population genomics

Myocardial tagging by Cardiovascular Magnetic Resonance: evolution of techniques--pulse sequences, analysis algorithms, and applications

Cardiovascular magnetic resonance (CMR) tagging has been established as an essential technique for measuring regional myocardial function. It allows quantification of local intramyocardial motion measures, e.g. strain and strain rate. The invention of CMR tagging came in the late eighties, where the technique allowed for the first time for visualizing transmural myocardial movement without having to implant physical markers. This new idea opened the door for a series of developments and improvements that continue up to the present time. Different tagging techniques are currently available that are more extensive, improved, and sophisticated than they were twenty years ago. Each of these techniques has different versions for improved resolution, signal-to-noise ratio (SNR), scan time, anatomical coverage, three-dimensional capability, and image quality. The tagging techniques covered in this article can be broadly divided into two main categories: 1) Basic techniques, which include magnetization saturation, spatial modulation of magnetization (SPAMM), delay alternating with nutations for tailored excitation (DANTE), and complementary SPAMM (CSPAMM); and 2) Advanced techniques, which include harmonic phase (HARP), displacement encoding with stimulated echoes (DENSE), and strain encoding (SENC). Although most of these techniques were developed by separate groups and evolved from different backgrounds, they are in fact closely related to each other, and they can be interpreted from more than one perspective. Some of these techniques even followed parallel paths of developments, as illustrated in the article. As each technique has its own advantages, some efforts have been made to combine different techniques together for improved image quality or composite information acquisition. In this review, different developments in pulse sequences and related image processing techniques are described along with the necessities that led to their invention, which makes this article easy to read and the covered techniques easy to follow. Major studies that applied CMR tagging for studying myocardial mechanics are also summarized. Finally, the current article includes a plethora of ideas and techniques with over 300 references that motivate the reader to think about the future of CMR tagging