Individuals with a heterozygous mutation at the ataxia-telangiectasia mutated gene ( ATM ) have been reported to be predisposed to ischemic heart disease. This report examined for the first time the effect of a heterozygous ATM mutation ( ATM ؉ / ؊ ) on plasma lipid levels and atherosclerosis intensity using, and ATM ؉ / ؊ / ApoE ؊ / ؊ mice. Our data demonstrated that the plasma cholesterol and triglyceride levels in ATM ؉ / ؊ and ATM ؉ / ؊ / LDLR ؊ / ؊ mice were approximately the same as those in ATM ؉ / ؉ and ATM ؉ / ؉ / LDLR ؊ / ؊ control mice, respectively. In contrast, the plasma cholesterol level was significantly higher in ATM ؉ / ؊ / ApoE ؊ / ؊ mice than in ATM ؉ / ؉ / ApoE ؊ / ؊ control mice. In addition, the ATM ؉ / ؊ / ApoE ؊ / ؊ mice showed higher plasma apoB-48 levels, slower clearance for plasma apoB-48-carrying lipoproteins, and more advanced atherosclerotic lesions in the aorta compared with the ATM ؉ / ؉ / ApoE ؊ / ؊ mice. These novel results suggest that the product of ATM is involved in an apoE-independent pathway for catabolism of apoB-48-carrying remnants; therefore, superimposition of a heterozygous ATM mutation onto an ApoE deficiency background reduces the clearance of apoB-48-carrying lipoproteins from the blood circulation and promotes the formation of atherosclerosis. The product of the ataxia-telangiectasia mutated gene ( ATM ) has been reported to be a nuclear protein and involved in several signaling pathways, including DNA damage recognition, cell cycle control, and meiotic recombination (for review, see 1). It is now known that a fraction of ATM is also present in the cytoplasm and associated with vesicular structures such as peroxisomes (2). Ataxiatelangiectasia patients [i.e., those individuals carrying mutations at both ATM alleles ( ATM Ϫ / Ϫ )] express a variety of progressive clinical symptoms, such as cerebellar ataxia, telangiectasias, and a high incidence of cancer (for review, see 3). Cells obtained from ataxia-telangiectasia patients are more sensitive to ionizing radiation and show increased chromosomal aberrations compared with those obtained from normal subjects (4). Individuals with an ATM mutation in one allele ( ATM ϩ / Ϫ ) are spared most of the symptoms of the disease but are predisposed to cancer (5). A close review of the literature suggests that heterozygous ATM deficiency might also increase the risk of atherosclerosis-related cardiovascular diseases. For example, Swift and Chase (6) reported that the age-related mortality of heterozygous ATM carriers was increased markedly compared with the general population and that ischemic heart disease was one of the underlying causes for the early death of these individuals. Ataxia-telangiectasia patients reportedly have increased plasma cholesterol and triglyceride levels (7), which are the two major risk factors for atherosclerosis. However, ataxia-telangiectasia patients do not usually live past 20 or 30 years of age, and atherosclerosis has not been studied in these individuals.More recently, a mouse mode...
Lipoprotein-associated phospholipase A2 (Lp-PLA2) and superoxide dismutase (SOD) are linked to regulating vascular/neuro-inflammation and stroke. Using a retrospective design, we investigated whether circulating Lp-PLA2 and SOD in cerebral small vessel disease (CSVD) patients were associated with cognitive impairment. Eighty-seven CSVD patients were recruited. Plasma Lp-PLA2 and SOD were determined, and cognitive status was measured by the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). The severity of white matter hypoerintensities (WMHs) in CSVD patients was rated according to Fazekas scales, and Lp-PLA2/SOD levels and MMSE/MoCA were compared. Multiple linear regressions were used to evaluate the relationship between Lp-PLA2 and SOD and the cognitive impairment. Ordinal logistic regression and generalized linear models (OLRGLMs) were applied to confirm whether Lp-PLA2 and SOD are independent risk factors for cognitive impairment in CVSD. Lp-PLA2 and SOD with mild or severe cognitive impairment were lower than those with normal congnition. Lp-PLA2 and SOD in CSVD patients with severe WMHs were significantly lower than those with mild or moderate WMH lesions. We noted positive linear associations of Lp-PLA and SOD with cognitive impairment in CSVD, independent of LDL-C. OLRGLMs confirmed that Lp-PLA2 and SOD were independent risk factors of cognitive impairment in CSVD. Lp-PLA2 and SOD are independently associated with cognitive impairment and WMH lesion, and may be useful for the rapid evaluation of cognitive impairment in CSVD. Lp-PLA2/SOD are modifiable factors that may be considered as therapeutic targets for preventing cognitive impairment in CSVD.
Optical coherence tomography (OCT) and OCT angiography (OCTA) enable noninvasive structural and angiographic imaging of the eye. Portable handheld OCT/OCTA systems are required for imaging patients in the supine position. Examples include infants in the neonatal intensive care unit (NICU) and operating room (OR). The speed of image acquisition plays a pivotal role in acquiring high-quality OCT/OCTA images, particularly with the handheld system, since both the operator hand tremor and subject motion can cause significant motion artifacts. In addition, having a large field of view and the ability of real-time data visualization are critical elements in rapid disease screening, reducing imaging time, and detecting peripheral retinal pathologies. The arrangement of optical components is less flexible in the handheld system due to the limitation of size and weight. In this paper, we introduce a 400-kHz, 55-degree field of view handheld OCT/OCTA system that has overcome many technical challenges as a portable OCT system as well as a high-speed OCTA system. We demonstrate imaging premature infants with retinopathy of prematurity (ROP) in the NICU, a patient with incontinentia pigmenti (IP), and a patient with X-linked retinoschisis (XLRS) in the OR using our handheld OCT system. Our design may have the potential for improving the diagnosis of retinal diseases and help provide a practical guideline for designing a flexible and portable OCT system.
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