Background: Pulmonary arterial hypertension (PAH) is a common complication for individuals with limited systemic sclerosis (lSSc). The identification and characterization of biomarkers for lSSc-PAH should lead to less invasive screening, a better understanding of pathogenesis, and improved treatment.

Methods And Findings: Forty-nine PBMC samples were obtained from 21 lSSc subjects without PAH (lSSc-noPAH), 15 lSSc subjects with PAH (lSSc-PAH), and 10 healthy controls; three subjects provided PBMCs one year later. Genome-wide gene expression was measured for each sample. The levels of 89 cytokines were measured in serum from a subset of subjects by Multi-Analyte Profiling (MAP) immunoassays. Gene expression clearly distinguished lSSc samples from healthy controls, and separated lSSc-PAH from lSSc-NoPAH patients. Real-time quantitative PCR confirmed increased expression of 9 genes (ICAM1, IFNGR1, IL1B, IL13Ra1, JAK2, AIF1, CCR1, ALAS2, TIMP2) in lSSc-PAH patients. Increased circulating cytokine levels of inflammatory mediators such as TNF-alpha, IL1-beta, ICAM-1, and IL-6, and markers of vascular injury such as VCAM-1, VEGF, and von Willebrand Factor were found in lSSc-PAH subjects.

Conclusions And Significance: The gene expression and cytokine profiles of lSSc-PAH patients suggest the presence of activated monocytes, and show markers of vascular injury and inflammation. These genes and factors could serve as biomarkers of PAH involvement in lSSc.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923145PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012106PLOS

Publication Analysis

Top Keywords

vascular injury
12
gene expression
12
limited systemic
8
systemic sclerosis
8
pulmonary arterial
8
arterial hypertension
8
lssc subjects
8
subjects pah
8
healthy controls
8
lssc-pah patients
8

Similar Publications

Background: Computed tomography angiography of the head (CTAH) is not routinely obtained during the initial evaluation of patients with traumatic intracranial hemorrhage (ICH); however, it is useful for diagnosing vascular pathologies that may have led to the bleed. The aims of this study were to identify traumatic ICH patient characteristics on presentation that are associated with positive CTAH findings to elucidate which ones should prompt a CTAH and compare outcomes of patients with positive and negative CTAH findings.

Methods: This is a retrospective cohort study of 522 patients who had blunt traumatic ICH and subsequently received CTAH between January 1, 2017, and January 1, 2022.

View Article and Find Full Text PDF

The diagnosis and management of acute traumatic diaphragmatic injury: A Western Trauma Association clinical decisions algorithm.

J Trauma Acute Care Surg

January 2025

From the Division of Acute Care Surgery, Department of Surgery (M.S., M.J.M.), Los Angeles General Medical Center, Los Angeles; Division of Acute Care Surgery, Department of Surgery (R.C.), Loma Linda University School of Medicine, Loma Linda, California; Division of Acute Care Surgery, Department of Surgery (C.A.C.), University of Florida College of Medicine, Gainesville, Florida; Division of Acute Care Surgery, Department of Surgery (C.F.), University of Maryland School of Medicine, Baltimore, Maryland; Division of Acute Care Surgery, Department of Surgery (J.H.), University of Kansas Medical Center, Kansas City, Kansas; Division of Acute Care Surgery, Department of Surgery (N.K.), University of Arizona College of Medicine-Phoenix, Phoenix, Arizona; Division of Acute Care Surgery, Department of Surgery (M.L.), Methodist Dallas Medical Center, Dallas, Texas; Division of Vascular Surgery and Endovascular Therapy (G.A.M.), Keck Medical Center of USC, Los Angeles, California; Division of Acute Care Surgery, Department of Surgery (L.J.M.), The University of Texas McGovern Medical School-Houston Red Duke Trauma Institute, Memorial Hermann Hospital, Houston, Texas; Division of Acute Care Surgery, Department of Surgery (A.R.P.), Medical University of South Carolina, North Charleston, South Carolina; Division of Acute Care Surgery, Department of Surgery (K.M.S.), Yale School of Medicine, New Haven, Connecticut; UCSF Department of Surgery at Zuckerberg San Francisco General Hospital (R.T.), University of California, San Francisco, San Francisco, California; Division of Acute Care Surgery, Department of Surgery (J.A.W.), St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Program in Trauma (D.M.S.), University of Maryland School of Medicine, Baltimore, Maryland.

View Article and Find Full Text PDF

The ε4 variant of human apolipoprotein E () is a key genetic risk factor for neurodegeneration in Alzheimer's disease and elevated all-cause mortality in humans. Understanding the factors and mechanisms that can mitigate the harmful effects of has significant implications. In this study, we find that inactivating the VHL-1 (Von Hippel-Lindau) protein can suppress mortality, neural and behavioral pathologies caused by transgenic human in .

View Article and Find Full Text PDF

Simulated microgravity predisposes kidney to injury through promoting intrarenal artery remodeling.

FASEB J

January 2025

Department of Nephrology, State Key Laboratory of Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, National Clinical Research Center for Kidney Diseases, Nephrology Institute of the Chinese People's Liberation Army, Chinese PLA General Hospital, Beijing, China.

Spaceflight-induced multi-organ dysfunction affects the health of astronauts and the safety of in-orbit flight. However, the effect of microgravity on the kidney and the underlying mechanisms are unknown. In the current study, we used a hindlimb unweighting (HU) animal model to simulate microgravity and employed histological analysis, ischemia-reperfusion experiments, renal ultrasonography, bioinformatics analysis, isometric force measurement, and other molecular experimental settings to evaluate the effects of microgravity on the kidneys and the underlying mechanisms involved in this transition.

View Article and Find Full Text PDF

CCN5 suppresses injury-induced vascular restenosis by inhibiting smooth muscle cell proliferation and facilitating endothelial repair via thymosin β4 and Cd9 pathway.

Eur Heart J

January 2025

State Key Laboratory of Cardiovascular Diseases and Medical Innovation Center, Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.

Background And Aims: Members of the CCN matricellular protein family are crucial in various biological processes. This study aimed to characterize vascular cell-specific effects of CCN5 on neointimal formation and its role in preventing in-stent restenosis (ISR) after percutaneous coronary intervention (PCI).

Methods: Stent-implanted porcine coronary artery RNA-seq and mouse injury-induced femoral artery neointima single-cell RNA sequencing were performed.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!