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Providence, RI, United States

Godfrey M.S.,Providence Medical Center | Jankowich M.D.,Vascular Research Laboratory
Chest | Year: 2016

Epidemiologic research has revealed a substantial portion of the general population with abnormal spirometry results that are characterized by decreased FEV1 and FVC but a preserved FEV1/FVC ratio. This restrictive spirometry pattern (RSP) is inconsistently defined in the literature and not well addressed by current guidelines; there is an accumulating body of evidence, however, that RSP is prevalent to a similar degree as airflow obstruction. Genetic and other risk factors for RSP, such as inhalational injuries and early life exposures, continue to be actively described. Although it seems that RSP is closely associated with the metabolic syndrome, diabetes, and systemic inflammation, it is not a simple marker of obesity. RSP is associated with adverse cardiovascular outcomes, as well as mortality, and it may be an underappreciated cause of functional impairments and respiratory symptoms. Improvement in outcomes in this population will require that clinicians have an appreciation for the significance of this spirometry pattern; additional research into the clinical and radiologic phenotype of these subjects is also needed. This article provides an overview of the recent developments in our understanding of this prevalent and highly morbid spirometry pattern. Copyright © 2016 American College of Chest Physicians. Published byElsevier Inc. All rights reserved.

Blanco-Colio L.M.,Vascular Research Laboratory
Frontiers in Immunology | Year: 2014

Cardiovascular diseases (CVD) are the first cause of mortality in Western countries. CVD include several pathologies such as coronary heart disease, stroke or cerebrovascular accident, congestive heart failure, peripheral arterial disease, and aortic aneurysm, among others. Interaction between members of the tumor necrosis factor (TNF) superfamily and their receptors elicits several biological actions that could participate in CVD. TNF-like weak inducer of apoptosis (TWEAK) and its functional receptor and fibroblast growth factor-inducible molecule 14 (Fn14) are two proteins belonging to the TNF superfamily that activate NF-κB by both canonical and non-canonical pathways and regulate several cell functions such as proliferation, migration, differentiation, cell death, inflammation, and angiogenesis. TWEAK/Fn14 axis plays a beneficial role in tissue repair after acute injury. However, persistent TWEAK/Fn14 activation mediated by blocking experiments or overexpression experiments in animal models has shown an important role of this axis in the pathological remodeling underlying CVD. In this review, we summarize the role of TWEAK/Fn14 pathway in the development of CVD, focusing on atherosclerosis and stroke and the molecular mechanisms by which TWEAK/Fn14 interaction participates in these pathologies. We also review the role of the soluble form of TWEAK as a biomarker for the diagnosis and prognosis of CVD. Finally, we highlight the results obtained with other members of the TNF superfamily that also activate canonical and non-canonical NF-κB pathway. © 2014 Blanco-Colio.

Ciborowski M.,University of San Pablo - CEU | Ciborowski M.,Medical University of Bialystok | Teul J.,University of San Pablo - CEU | Teul J.,Medical University of Bialystok | And 5 more authors.
PLoS ONE | Year: 2012

Abdominal aortic aneurysm (AAA) is a permanent and localized aortic dilation, defined as aortic diameter ≥3 cm. It is an asymptomatic but potentially fatal condition because progressive enlargement of the abdominal aorta is spontaneously evolving towards rupture. Biomarkers may help to explain pathological processes of AAA expansion, and allow us to find novel therapeutic strategies or to determine the efficiency of current therapies. Metabolomics seems to be a good approach to find biomarkers of AAA. In this study, plasma samples of patients with large AAA, small AAA, and controls were fingerprinted with LC-QTOF-MS. Statistical analysis was used to compare metabolic fingerprints and select metabolites that showed a significant change. Results presented here reveal that LC-QTOF-MS based fingerprinting of plasma from AAA patients is a very good technique to distinguish small AAA, large AAA, and controls. With the use of validated PLS-DA models it was possible to classify patients according to the disease stage and predict properly the stage of additional AAA patients. Identified metabolites indicate a role for sphingolipids, lysophospholipids, cholesterol metabolites, and acylcarnitines in the development and progression of AAA. Moreover, guanidinosuccinic acid, which mimics nitric oxide in terms of its vasodilatory action, was found as a strong marker of large AAA. © 2012 Ciborowski et al.

Jankowich M.D.,Vascular Research Laboratory | Jankowich M.D.,Brown University | Rounds S.,Vascular Research Laboratory | Rounds S.,Brown University
Lung | Year: 2010

Studies have described individuals with combined pulmonary fibrosis and emphysema (CPFE), with preserved lung volumes, significant reductions in gas exchange, and high prevalence of pulmonary hypertension. While physiologic changes in CPFE are well documented, there is little mortality data in the CPFE population compared to appropriate controls. A study was performed to determine the features and outcomes of a group of individuals with imaging and/or pathologic evidence of CPFE to determine if individuals with combined pulmonary fibrosis and emphysema have different features and survival than individuals with pulmonary fibrosis alone. We conducted a retrospective study at a Veterans Affairs Medical Center. Included in the study were individuals hospitalized over a 5-year period who were given a clinical diagnosis of pulmonary fibrosis. Individuals with confirmed imaging or pathologic evidence of pulmonary fibrosis were divided into a study group with concomitant emphysema (CPFE group, n = 20) and a control group without emphysema (isolated pulmonary fibrosis (PF) group, n = 24). The CPFE group, all current or former cigarette smokers, had significantly larger lung volumes, more expiratory airflow obstruction, and worse gas exchange than the isolated pulmonary fibrosis group. Mortality did not differ between the groups. Combined pulmonary fibrosis and emphysema results in unique physiologic features but no difference in survival compared with a group with pulmonary fibrosis alone. © 2010 US Government.

Patel S.R.,Vascular Research Laboratory | Bellary S.,Aston University | Qin L.,Vascular Research Laboratory | Balanos G.M.,University of Birmingham | And 2 more authors.
Investigative Ophthalmology and Visual Science | Year: 2012

Purpose. To investigate the relationship between vascular function parameters measured at the retinal and systemic level and known markers for cardiovascular risk in patients with impaired glucose tolerance (IGT).Methods. Sixty age- and sex-matched white European adults (30 with IGT and 30 with normal glucose tolerance [NGT]) were recruited for the study. Fasting plasma glucose, lipids, and 24-hour blood pressure (BP) were measured in all subjects. Systemic vascular and endothelial function was assessed by using carotid-artery intimal media thickness (cIMT) and flow-mediated dilation (FMD). Retinal vascular reactivity was assessed by the dynamic retinal vessel analyzer. Additionally, blood glutathione (reduced glutathione [GSH], glutathione disulfide [GSSG], and total glutathione [tGSH]) and plasma von Willebrand (vWF) factor levels were also measured. Results. Individuals with IGT demonstrated higher BP values (P < 0.001), fasting triglyceride (TG) levels and TG:high-density lipoprotein (HDL) ratios (P < 0.001) than NGT subjects. Furthermore, total:HDL-cholesterol (HDL-C) ratios and Framingham scores were raised (P 1/4 0.010 and P < 0.001, respectively). Blood glutathione levels (GSH, GSSG, and tGSH) were lower (P < 0.001, P1/40.039, and P < 0.001, respectively) while plasma vWF was increased (P 1/4 0.014) in IGT subjects compared to controls. IGT individuals also demonstrated higher IMT in right and left carotid arteries (P 1/4 0.017 and P 1/4 0.005, respectively) alongside larger brachial artery diameter (P1/40.015) and lower FMD percentage (P1/40.026) and glyceryl trinitrate-induced dilation (P1/40.012) than healthy controls. At the retinal arterial level, the IGT subjects showed higher baseline diameter fluctuations (BDFs) (P 1/4 0.026), longer reaction time (RT) (P 1/40.032), and reduced baseline-corrected flicker response (bFR) (P1/40.045). In IGT subjects, retinal BDF correlated with total:HDL (P 1/4 0.003) and HDL-C (P 1/4 0.004). Arterial RTalso correlated with FMD (P1/40.017) in IGT but not NGT subjects. Conclusions. In IGT individuals there is a relationship between macro- and microvascular function, as well as a direct correlation between the observed retinal microcirculatory changes and established plasma markers for cardiovascular diseases. Multifactorial preventive interventions to decrease vascular risk in these individuals should be considered. © 2012 The Association for Research in Vision and Ophthalmology, Inc.

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