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| 13. |
- Graslund, S, et al.
(författare)
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Protein production and purification
- 2008
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Ingår i: Nature methods. - : Springer Science and Business Media LLC. - 1548-7105 .- 1548-7091. ; 5:2, s. 135-146
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Tidskriftsartikel (refereegranskat)
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| 16. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 21. |
- Darabi, H, et al.
(författare)
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Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs)
- 2016
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 32512-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.92; CI 0.90–0.94; P = 8.96 × 10−15)) and are correlated with two previously reported risk-associated variants at this locus, SNPs rs6504950 (OR = 0.94, P = 2.04 × 10−09, r2 = 0.73 with lead SNP) and rs1156287 (OR = 0.93, P = 3.41 × 10−11, r2 = 0.83 with lead SNP). Analyses indicate only one causal SNP in the region and several enhancer elements targeting STXBP4 are located within the 53 kb association signal. Expression studies in breast tumor tissues found SNP rs2787486 to be associated with increased STXBP4 expression, suggesting this may be a target gene of this locus.
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| 24. |
- Shu, Xiang, et al.
(författare)
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Associations of obesity and circulating insulin and glucose with breast cancer risk : a Mendelian randomization analysis
- 2019
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Ingår i: International Journal of Epidemiology. - : OXFORD UNIV PRESS. - 0300-5771 .- 1464-3685. ; 48:3, s. 795-806
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Tidskriftsartikel (refereegranskat)abstract
- Background: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. Methods: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. Results: All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p = 5.09 x 10(-4)], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p = 4.02 x 10(-4)), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p = 5.05 x 10(-19)) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p = 9.22 x 10(-6)). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. Conclusions: We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer.
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- Fung, P. P. L., et al.
(författare)
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Time to onset of bisphosphonate-related osteonecrosis of the jaws : a multicentre retrospective cohort study
- 2017
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Ingår i: Oral Diseases. - : WILEY. - 1354-523X .- 1601-0825. ; 23:4, s. 477-483
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of bisphosphonates (BP). Although the risk of ONJ increases with increasing duration of BP treatment, there are currently no reliable estimates of the ONJ time to onset (TTO). The objective of this study was to estimate the TTO and associated risk factors in BP-treated patients.Subjects and Methods: Retrospective analysis of data from 22 secondary care centres in seven countries relevant to 349 patients who developed BP-related ONJ between 2004 and 2012.Results: The median (95%CI) TTO was 6.0 years in patients treated with alendronate (n=88) and 2.2years in those treated with zoledronate (n=218). Multivariable Cox regression showed that dentoalveolar surgery was inversely associated, and the use of antiangiogenics directly associated, with the TTO in patients with cancer treated with zoledronate.Conclusions: The incidence of ONJ increases with the duration of BP therapy, with notable differences observed with respect to BP type and potency, route of administration and underlying disease. When data are stratified by BP type, a time of 6.0 and 2.2years of oral alendronate and intravenous zoledronate therapy, respectively, is required for 50% of patients to develop ONJ. After stratification by disease, a time of 5.3 and 2.2years of BP therapy is required for 50% of patients with osteoporosis and cancer, respectively, to develop ONJ. These findings have significant implications for the design of future clinical studies and the development of risk-reduction strategies aimed at either assessing or modulating the risk of ONJ associated with BP.
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| 27. |
- Pelttari, LM, et al.
(författare)
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RAD51B in Familial Breast Cancer
- 2016
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5, s. e0153788-
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Tidskriftsartikel (refereegranskat)
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| 31. |
- Zeng, Chenjie, et al.
(författare)
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Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus
- 2016
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.
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| 32. |
- Choularton, T. W., et al.
(författare)
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The Great Dun Fell Cloud Experiment 1993 : An overview
- 1997
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Ingår i: Atmospheric Environment. - 1352-2310. ; 31:16, s. 2393-2405
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Tidskriftsartikel (refereegranskat)abstract
- The 1993 Ground-based Cloud Experiment on Great Dun Fell used a wide range of measurements of trace gases, aerosol particles and cloud droplets at five sites to study their sources and sinks especially those in cloud. These measurements have been interpreted using a variety of models. The conclusions add to our knowledge of air pollution, acidification of the atmosphere and the ground, eutrophication and climate change. The experiment is designed to use the hill cap cloud as a flow-through reactor, and was conducted in varying levels of pollution typical of much of the rural temperate continental northern hemisphere in spring-time.
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| 33. |
- Couch, Fergus J., et al.
(författare)
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Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
- 2016
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
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| 37. |
- Landin-Olsson, Mona, et al.
(författare)
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Immunoreactive trypsin(Ogen) in the sera of children with recent-onset insulin-dependent diabetes and matched controls
- 1990
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Ingår i: Pancreas. - : Ovid Technologies (Wolters Kluwer Health). - 0885-3177. ; 5:3, s. 241-247
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the exocrine pancreatic function at the time of diagnosis of insulin-dependent diabetes mellitus, we determined immunoreactive an-odal and cathodal trypsin(ogen) levels in sera from almost all children (n = 375) 0-14 years of age in Sweden in whom diabetes developed during 1 year, and in sex-, age-, and geographically matched control subjects (n = 312). The median level of anodal trypsin(ogen) was 5 (quartile range, 3-7) µg/L in children with newly diagnosed diabetes, compared with a median level of 7 (quartile range, 4-8) µg/L in control subjects (p < 0.0001). Similarly, the median level of cathodal trypsin(ogen) was 8 (quartile range, 4-10) µg/L in children with diabetes, compared with a median level of 11 (quartile range, 7-15) µg/L in control subjects (p < 0.0001). The median of the individual ratios between cathodal and anodal trypsin(ogen) was 1.4 in the diabetic patients and 1.7 in the control children (p < 0.001). In a multivariate test, however, only the decrease in cathodal trypsin(ogen) concentration was associated with diabetes. The levels of trypsin(ogen)s did not correlate with levels of islet cell antibodies, present in 81% of the diabetic children. Several mechanisms may explain our findings, for example, similar pathogenetic factors may affect both the endocrine and exocrine pancreas simultaneously, a failing local trophic stimulation by insulin on the exocrine cells may decrease the trypsinogen production, and there may be an increased elimination of trypsin(ogen) because of higher filtration through the kidneys in the hyperglycemic state.
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| 40. |
- Rydberg, Lennart, 1944, et al.
(författare)
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Extracorporeal ("ex vivo") connection of pig kidneys to humans. II. The anti-pig antibody response.
- 1996
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Ingår i: Xenotransplantation. - : Wiley. - 0908-665X .- 1399-3089. ; 3:4, s. 340-53
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Tidskriftsartikel (refereegranskat)abstract
- Pig kidneys were extracorporeally "ex vivo" connected to the circulation of two volunteer male dialysis patients (Breimer et al., this issue). The patients were pretreated by daily plasmapheresis for 3 consecutive days, which reduced the anti-pig lymphocytotoxic titer from 8 to 2 in the first patient and from 8 to 1 in the second patient. The anti-pig hemagglutinating titers were reduced from 32 to 4 in the first patient and from 2 to 1 in the second patient. No drugs, except heparin, were given. The perfusion lasted for 65 min in patient 1 and the experiment was terminated due to increased vascular resistance in the pig kidney. Ultrastructural investigation showed a picture similar to a hyperacute vascular rejection. Immunohistochemical studies showed a weak staining of IgM antibodies, but no IgG in the small arteries and glomeruli. The pig kidney of patient 2 was perfused for 15 min and the experiment terminated due to serious side effects of the patient. Light and electron microscopical investigation showed virtually no structural changes of the kidney tissue and immunostaining for human antibodies was negative. In both patients, serum samples collected 2-5 weeks postperfusion showed a strong anti-pig antibody titer rise (up to 512) which thereafter declined but stabilized on a higher level than before the experiment. The antibody response in the two patients was different. In patient 1, the major anti-pig antibodies directed to carbohydrate antigens were of IgG (IgG1 and IgG2 subclasses) type, while the IgM response was less prominent and virtually no IgA antibodies were produced. Despite the short duration of the perfusion in patient 2, a humoral immune response was seen that was mainly confined to the IgA immunoglobulin class (IgA1 subclass). Blood group glycospingolipid fractions, prepared from the contralateral kidney of the donor pigs, were used for immunostaining with patient serum samples. In both patients, the antibodies produced after the perfusion, mainly recognized the Galα1-3Gal epitope both as part of the "linear B" pentasaccharide but also on more complex carbohydrate structures. Patient 1 was HLA-immunized before the experiment due to a kidney allograft and had a panel reactivity of 85% before the perfusion. No change in the panel reactivity of HLA-antibodies was found after the perfusion experiments. Patient 2 had no HLA antibodies before and remained negative after the perfusion. Patient serum samples collected before and after the perfusion were tested for reactivity against human endothelial cell lines. No antibodies were generated.
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| 42. |
- Andersson, Pia, et al.
(författare)
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Oral health and nutritional status in a group of geriatric rehabilitation patients
- 2002
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Ingår i: Scandinavian Journal of Caring Sciences. - : Wiley-Blackwell. - 0283-9318 .- 1471-6712. ; 16:3, s. 311-318
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Tidskriftsartikel (refereegranskat)abstract
- The aims of this study were to evaluate the oral health status and nutritional status in a group of geriatric rehabilitation patients, and to analyse the relationship between these two parameters. Nurses at the ward performed structured assessments of oral and nutritional status using the Revised Oral Assessment Guide and the Subjective Global Assessment form in 223 newly admitted patients. Most oral health problems were found among patients who stayed longer at the hospital and were more dependent on help as compared with the healthier patients. Thirty-four per cent of the patients were either severely undernourished, at risk or suspected to be undernourished (UN). Oral health problems were more common among UN patients (p < 0.0005) compared with well-nourished patients. The most frequent oral health problem was found on teeth or dentures (48%). Problems related to the tongue and lips were also common among UN patients (56 and 44%, respectively). Oral health status was correlated (r = 0.32) to nutritional status. Problems with swallowing had the strongest association to the nutritional status (OR 6.05; 95% CI 2.41-15.18). This study demonstrated that poor oral health status was related to undernourishment.
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| 43. |
- Andersson, Pia, et al.
(författare)
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Oral health problems in elderly rehabilitation patients
- 2004
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Ingår i: International Journal of Dental Hygiene. - : Wiley-Blackwell. - 1601-5029 .- 1601-5037. ; 2:2, s. 70-77
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Tidskriftsartikel (refereegranskat)abstract
- A combination of poor oral hygiene and dry mouth may be hazardous to the oral health status. However, systematic assessments in order to detect oral health problems are seldom performed in the nursing care of the elderly. The aims of this study were to investigate the occurrence of oral health problems measured using the Revised Oral Assessment Guide (ROAG) and to analyse associations between oral health problems and age, gender, living conditions, cohabitation, reason for admission, number of drugs, and functional and nutritional status. One registered nurse performed oral health assessments using ROAG in 161 newly admitted elderly patients in rehabilitation care. Oral health problems were found in 71% of the patients. Thirty per cent of these patients had between four and eight problems. Low saliva flow and problems related to lips were the most frequent oral health problems. Problems in oral health status were significantly associated with presence of respiratory diseases (problems with gums, lips, alterations on the tongue and mucous membranes), living in special accommodation (low saliva flow, problems with teeth/dentures and alterations on the tongue), being undernourished (alterations on the tongue and low saliva flow) and being a woman (low saliva flow). The highest Odds ratio (OR) was found in problems with gums in relation with prevalence of respiratory diseases (OR 8.9; confidence interval (CI) 2.8–27.8; P < 0.0005). This study indicates the importance of standardised oral health assessments in order to detect oral health problems which can otherwise be hidden when the patients are admitted to the hospital ward.
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| 45. |
- Banefelt, J., et al.
(författare)
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Work productivity loss and indirect costs associated with new cardiovascular events in high-risk patients with hyperlipidemia: estimates from population-based register data in Sweden
- 2016
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Ingår i: European Journal of Health Economics. - : SPRINGER. - 1618-7598 .- 1618-7601. ; 17:9, s. 1117-1124
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To estimate productivity loss and associated indirect costs in high-risk patients treated for hyperlipidemia who experience cardiovascular (CV) events. Methods Retrospective population-based cohort study conducted using Swedish medical records linked to national registers. Patients were included based on prescriptions of lipid-lowering therapy between 1 January 2006 and 31 December 2011 and followed until 31 December 2012 for identification of CV events and estimation of work productivity loss (sick leave and disability pension) and indirect costs. Patients were stratified into two cohorts based on CV risk level: history of major cardiovascular disease (CVD) and coronary heart disease (CHD) risk equivalent. Propensity score matching was applied to compare patients with new events (cases) to patients without new events (controls). The incremental effect of CV events was estimated using a difference-in-differences design, comparing productivity loss among cases and controls during the year before and the year after the cases event. Results The incremental effect on indirect costs was largest in the CHD risk equivalent cohort (n = 2946) at (sic)3119 (P value amp;lt;0.01). The corresponding figure in the major CVD history cohort (n = 4508) was (sic)2210 (P value amp;lt;0.01). There was substantial variation in productivity loss depending on the type of event. Transient ischemic attack and revascularization had no significant effect on indirect costs. Myocardial infarction ((sic)), unstable angina ((sic)) and, most notably, ischemic stroke ((sic)) yielded substantial incremental cost estimates (P values amp;lt;0.01). Conclusions Indirect costs related to work productivity losses of CV events are substantial in Swedish high-risk patients treated for hyperlipidemia and vary considerably by type of event.
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| 47. |
- Bosnyak, S., et al.
(författare)
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Stimulation of angiotensin AT(2) receptors by the non-peptide agonist, Compound 21, evokes vasodepressor effects in conscious spontaneously hypertensive rats
- 2010
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Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 159:3, s. 709-716
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Angiotensin type 2 receptor (AT(2) receptor) stimulation evokes vasodilator effects in vitro and in vivo that oppose the vasoconstrictor effects of angiotensin type 1 receptors (AT(1) receptors). Recently, a novel non-peptide AT(2) receptor agonist, Compound 21, was described, which exhibited high AT(2) receptor selectivity. Experimental approach: Functional cardiovascular effects of the drug candidate Compound 21 were assessed, using mouse isolated aorta and rat mesenteric arteries in vitro and in conscious spontaneously hypertensive rats (SHR). Key results: Compound 21 evoked dose-dependent vasorelaxations in aortic and mesenteric vessels, abolished by the AT(2) receptor antagonist, PD123319. In vivo, Compound 21 administered alone, at doses ranging from 50 to 1000 ng center dot kg-1 center dot min-1 over 4 h did not decrease blood pressure in conscious normotensive Wistar-Kyoto rats or SHR. However, when given in combination with the AT(1) receptor antagonist, candesartan, Compound 21 (300 ng center dot kg-1 center dot min-1) lowered blood pressure in SHR only. Further analysis in separate groups of conscious SHR revealed that, at a sixfold lower dose, Compound 21 (50 ng center dot kg-1 center dot min-1) still evoked a significant depressor response in adult SHR (similar to 30 mmHg) when combined with different doses of candesartan (0.01 or 0.1 mg center dot kg-1). Moreover, the Compound 21-evoked depressor effect was abolished when co-infused (50 mu g center dot kg-1 center dot min-1 for 2 h) with the AT(2) receptor antagonist PD123319. Conclusion and implications: Collectively, our results indicate that acute administration of Compound 21 evoked blood pressure reductions via AT(2) receptor stimulation. Thus Compound 21 can be considered an excellent drug candidate for further study of AT(2) receptor function in cardiovascular disease.
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| 48. |
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| 49. |
- Cakir, B., et al.
(författare)
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Thrombocytopenia is associated with severe retinopathy of prematurity
- 2018
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Ingår i: Jci Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 3:19
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Tidskriftsartikel (refereegranskat)abstract
- Retinopathy of prematurity (ROP) is characterized by abnormal retinal neovascularization in response to vessel loss. Platelets regulate angiogenesis and may influence ROP progression. In preterm infants, we assessed ROP and correlated with longitudinal postnatal platelet counts (n = 202). Any episode of thrombocytopenia (< 100 x 10(9)/l) at >= 30 weeks postmenstrual age (at onset of ROP) was independently associated with severe ROP, requiring treatment. Infants with severe ROP also had a lower weekly median platelet count compared with infants with less severe ROP. In a mouse oxygen-induced retinopathy model of ROP, platelet counts were lower at P17 (peak neovascularization) versus controls. Platelet transfusions at P15 and P16 suppressed neovascularization, and platelet depletion increased neovascularization. Platelet transfusion decreased retinal of vascular endothelial growth factor A (VEGFA) mRNA and protein expression; platelet depletion increased retinal VEGFA mRNA and protein expression. Resting platelets with intact granules reduced neovascularization, while thrombin-activated degranulated platelets did not. These data suggest that platelet releasate has a local antiangiogenic effect on endothelial cells to exert a downstream suppression of VEGFA in neural retina. Low platelet counts during the neovascularization phase in ROP is significantly associated with the development of severe ROP in preterm infants. In a murine model of retinopathy, platelet transfusion during the period of neovascularization suppressed retinopathy.
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