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Linking LOXL2 to Cardiac Interstitial Fibrosis.

ABSTRACT: Cardiovascular diseases (CVDs) are the leading causes of death worldwide. CVD pathophysiology is often characterized by increased stiffening of the heart muscle due to fibrosis, thus resulting in diminished cardiac function. Fibrosis can be caused by increased oxidative stress and inflammation, which is strongly linked to lifestyle and environmental factors such as diet, smoking, hyperglycemia, and hypertension. These factors can affect gene expression through epigenetic modifications. Lysyl oxidase like 2 (LOXL2) is responsible for collagen and elastin cross-linking in the heart, and its dysregulation has been pathologically associated with increased fibrosis. Additionally, studies have shown that, LOXL2 expression can be regulated by DNA methylation and histone modification. However, there is a paucity of data on LOXL2 regulation and its role in CVD. As such, this review aims to gain insight into the mechanisms by which LOXL2 is regulated in physiological conditions, as well as determine the downstream effectors responsible for CVD development.

SUBMITTER: Erasmus M

PROVIDER: S-EPMC7460598 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Linking LOXL2 to Cardiac Interstitial Fibrosis.

Erasmus Melisse M Samodien Ebrahim E Lecour Sandrine S Cour Martin M Lorenzo Oscar O Dludla Phiwayinkosi P Pheiffer Carmen C Johnson Rabia R

International journal of molecular sciences 20200818 16

Cardiovascular diseases (CVDs) are the leading causes of death worldwide. CVD pathophysiology is often characterized by increased stiffening of the heart muscle due to fibrosis, thus resulting in diminished cardiac function. Fibrosis can be caused by increased oxidative stress and inflammation, which is strongly linked to lifestyle and environmental factors such as diet, smoking, hyperglycemia, and hypertension. These factors can affect gene expression through epigenetic modifications. Lysyl oxi ...[more]

PMID: 32824630

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Project description:BACKGROUND:Myocardial fibrosis leads to impaired cardiac function and events. Extracellular volume fraction (ECV) assessed with an iodinated contrast agent and measured by cardiac CT may be a useful noninvasive marker of fibrosis. OBJECTIVE:The purpose of this study was to develop and evaluate a 3-dimensional (3D) ECV calculation toolkit (ECVTK) for ECV determination by cardiac CT. METHODS:Twenty-four subjects (10 systolic heart failure, age, 60 ± 17 years; 5 diastolic failure, age 56 ± 20 years; 9 matched healthy subjects, age 59 ± 7 years) were evaluated. Cardiac CT examinations were done on a 320-multidetector CT scanner before and after 130 mL of iopamidol (Isovue-370; Bracco Diagnostics, Plainsboro, NJ, USA) was administered. A calcium score type sequence was performed before and 7 minutes after contrast with single gantry rotation during 1 breath hold and single cardiac phase acquisition. ECV was calculated as (?HUmyocardium/?HUblood) × (1 - Hct) where Hct is the hematocrit, and ?HU is the change in Hounsfield unit attenuation = HUafter iodine - HUbefore iodine. Cardiac magnetic resonance imaging was performed to assess myocardial structure and function. RESULTS:Mean 3D ECV values were significantly higher in the subjects with systolic heart failure than in healthy subjects and subjects with diastolic heart failure (mean, 41% ± 6%, 33% ± 2%, and 35% ± 5%, respectively; P = 0.02). Interobserver and intraobserver agreements were excellent for myocardial, blood pool, and ECV (intraclass correlation coefficient, >0.90 for all). Higher 3D ECV by cardiac CT was associated with reduced systolic circumferential strain, greater end-diastolic and -systolic volumes, and lower ejection fraction (r = 0.70, r = 0.60, r = 0.73, and r = -0.68, respectively; all P < 0.001). CONCLUSION:3D ECV by cardiac CT can be performed with ECVTK. We demonstrated increased ECV in subjects with systolic heart failure compared with healthy subjects. Cardiac CT results also showed good correlation with important functional heart biomarkers, suggesting the potential for myocardial tissue characterization with the use of 3D ECV by cardiac CT. This trial is registered at www.ClinicalTrials.gov as NCT01160471.

Dataset Information

Linking LOXL2 to Cardiac Interstitial Fibrosis.

Publications

Linking LOXL2 to Cardiac Interstitial Fibrosis.

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