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Fibrosis-related biomarkers and large and small vessel disease: the Cardiovascular Health Study.

ABSTRACT: Fibrosis has been implicated in a number of pathological, organ-based conditions of the liver, kidney, heart, and lungs. The objective of this study was to determine whether biomarkers of fibrosis are associated with vascular disease in the large and/or small vessels.We evaluated the associations of two circulating biomarkers of fibrosis, transforming growth factor-? (TGF-?) and procollagen type III N-terminal propeptide (PIIINP), with incident peripheral artery disease (PAD) and subclinical macrovascular (carotid intima-media thickness, flow-mediated vasodilation, ankle-brachial index, retinal vein diameter), and microvascular (retinal artery diameter and retinopathy) disease among older adults in the Cardiovascular Health Study. We measured TGF-? and PIIINP from samples collected in 1996 and ascertained clinical PAD through 2011. Measurements of large and small vessels were collected between 1996 and 1998.After adjustment for sociodemographic, clinical, and biochemical risk factors, TGF-? was associated with incident PAD (hazard ratio [HR] = 1.36 per doubling of TGF-?, 95% confidence interval [CI] = 1.04, 1.78) and retinal venular diameter (1.63 ?m per doubling of TGF-?, CI = 0.23, 3.02). PIIINP was not associated with incident PAD, but was associated with carotid intima-media thickness (0.102 mm per doubling of PIIINP, CI = 0.029, 0.174) and impaired brachial artery reactivity (-0.20% change per doubling of PIIINP, CI = -0.39, -0.02). Neither TGF-? nor PIIINP were associated with retinal arteriolar diameter or retinopathy.Serum concentrations of fibrosis-related biomarkers were associated with several measures of large vessel disease, including incident PAD, but not with small vessel disease. Fibrosis may contribute to large vessel atherosclerosis in older adults.

SUBMITTER: Agarwal I

PROVIDER: S-EPMC4517825 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Fibrosis-related biomarkers and large and small vessel disease: the Cardiovascular Health Study.

Agarwal Isha I Arnold Alice A Glazer Nicole L NL Barasch Eddy E Djousse Luc L Fitzpatrick Annette L AL Gottdiener John S JS Ix Joachim H JH Jensen Richard A RA Kizer Jorge R JR Rimm Eric B EB Siscovick David S DS Tracy Russell P RP Wong Tien Y TY Mukamal Kenneth J KJ

Atherosclerosis 20150216 2

<h4>Objective</h4>Fibrosis has been implicated in a number of pathological, organ-based conditions of the liver, kidney, heart, and lungs. The objective of this study was to determine whether biomarkers of fibrosis are associated with vascular disease in the large and/or small vessels.<h4>Methods</h4>We evaluated the associations of two circulating biomarkers of fibrosis, transforming growth factor-β (TGF-β) and procollagen type III N-terminal propeptide (PIIINP), with incident peripheral artery ...[more]

PMID: 25725316

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Project description:BackgroundHomozygous or compound heterozygous mutations in high temperature requirement serine peptidase A1 (HTRA1) gene are responsible for cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Recently, increasing evidence has shown that heterozygous HTRA1 mutations are also associated with cerebral small vessel disease (CSVD) with an autosomal dominant pattern of inheritance. This study was aimed to analyze the genetic and clinical characteristics of HTRA1-related autosomal dominant CSVD.MethodsWe presented three new Chinese cases of familial CSVD with heterozygous HTRA1 mutations and reviewed all clinical case reports and articles on HTRA1-related autosomal dominant CSVD included in PUBMED by the end of March 1, 2020. CARASIL probands with genetic diagnosis reported to date were also reviewed. The genetic and clinical characteristics of HTRA1-related autosomal dominant CSVD were summarized and analyzed by comparing with CARASIL.ResultsForty-four HTRA1-related autosomal dominant CSVD probands and 22 CARASIL probands were included. Compared with typical CARASIL, HTRA1-related autosomal dominant probands has a higher proportion of vascular risk factors (P < 0.001), a later onset age (P < 0.001), and a relatively slower clinical progression. Alopecia and spondylosis can be observed, but less than those in the typical CARASIL. Thirty-five heterozygous mutations in HTRA1 were reported, most of which were missense mutations. Amino acids located close to amino acids 250-300 were most frequently affected, followed by these located near 150∼200. While amino acids 250∼300 were also the most frequently affected region in CARASIL patients, fewer mutations precede the 200th amino acids were detected, especially in the Kazal-type serine protease domain.ConclusionsHTRA1-related autosomal dominant CSVD is present as a mild phenotype of CARASIL. The trend of regional concentration of mutation sites may be related to the concentration of key sites in these regions which are responsible for pathogenesis of HTRA1-related autosomal dominant CSVD.

Dataset Information

Fibrosis-related biomarkers and large and small vessel disease: the Cardiovascular Health Study.

Publications

Fibrosis-related biomarkers and large and small vessel disease: the Cardiovascular Health Study.

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