| 1. |
|
|
| 2. |
- Gonçalves, Isabel, et al.
(author)
-
Osteomodulin Gene Expression Is Associated with Plaque Calcification, Stability, and Fewer Cardiovascular Events in the CPIP Cohort
- 2022
-
In: Stroke. - 0039-2499 .- 1524-4628. ; 53:3, s. 79-84
-
Journal article (peer-reviewed)abstract
- Background: Stable atherosclerotic plaques are characterized by thick fibrous caps of smooth muscle cells, collagen, and macrocalcifications. Identifying factors of plaque stability is necessary to design drugs to prevent plaque rupture and symptoms. Osteomodulin, originally identified in bones, is expressed by bone synthesizing osteoblasts and involved in mineralization. In the present study, we analyzed osteomodulin expression in human carotid plaques, its link with plaque phenotype, calcification, and future cardiovascular events. Methods: Osteomodulin gene expression (OMD; n=82) was determined by RNA sequencing and osteomodulin protein levels by immunohistochemistry (n=45) in carotid plaques obtained by endarterectomy from patients with or without cerebrovascular symptoms from the CPIP (Carotid Plaque Imaging Project) cohort, Skåne University Hospital, Sweden. Plaque components were assessed by immunohistochemistry, RNA sequencing, and multiplex analysis. Patients were followed for cardiovascular events or cardiovascular death during a median of 57 or 70 months, respectively, using national registers. Results: OMD levels were increased in plaques from asymptomatic patients compared to symptomatics. High OMD levels were associated with fewer cardiovascular events during follow-up. OMD correlated positively with smooth muscle α-actin (ACTA2; r=0.73, P=10-13) and collagen (COL1A2; r=0.4, P=0.0002), but inversely with CD68 gene expression (r=-0.67, P=10-11), lipids (r=-0.37, P=0.001), intraplaque hemorrhage (r=-0.32, P=0.010), inflammatory cytokine, and matrix metalloproteinase plaque contents. OMD was positively associated with MSX2 (Msh Homeobox 2) (r=0.32, P=0.003), a marker of preosteoblast differentiation, BMP4 (bone morphogenetic protein) (r=0.50, P=0.000002) and BMP6 (r=0.47, P=0.000007), plaque calcification (r=0.35, P=0.016), and was strongly upregulated in osteogenically stimulated smooth muscle cells, which was further increased upon BMP stimulation. Osteomodulin protein was present in calcified regions. Osteomodulin protein levels were associated with plaque calcification (r=0.41, P=0.006) and increased in macrocalcified plaques. Conclusions: These data show that osteomodulin mRNA and protein levels are associated with plaque calcification in human atherosclerosis. Furthermore, osteomodulin mRNA, but not protein levels, is associated with plaque stability.
|
|
| 3. |
|
|
| 4. |
- Edsfeldt, Andreas, et al.
(author)
-
Low carotid calcium score is associated with higher levels of glycosaminoglycans, tumor necrosis factor-alpha, and parathyroid hormone in human carotid plaques.
- 2011
-
In: Stroke: a journal of cerebral circulation. - 1524-4628. ; 42:10, s. 458-2966
-
Journal article (peer-reviewed)abstract
- BACKGROUND AND PURPOSE: Computed tomography (CT) is used to study coronary artery plaques, but little is known about its potential to characterize plaque composition. This study assesses the relation between carotid calcium score (CCS) by CT and plaque composition, namely extracellular matrix, inflammatory mediators, and calcium metabolites. METHODS: Thirty patients with significant carotid stenosis underwent preoperative CT. CCS was quantified by Agaston calcium score. Plaque components were studied histologically and biochemically (collagen, elastin, and glycosaminoglycans). Fraktalkine, interferon-γ, interleukin-10, interleukin-12 p70, interleukin-1β, interleukin-6, monocyte chemoattractant protein-1, platelet-derived growth factor-AB/BB, RANTES and tumor necrosis factor-α, and parathyroid hormone were measured using Luminex technology. RESULTS: Plaques with CCS ≥400 had more calcium (P=0.012), less glycosaminoglycan (P=0.002), tumor necrosis factor-α (P=0.013), and parathyroid hormone (P=0.028) than those with CCS <400. CCS correlated with plaque content of calcium (r=0.62; P<0.001) and inversely with glycosaminoglycan (r=-0.49; P=0.006) and tumor necrosis factor-α (r=-0.56; P=0.001). CONCLUSIONS: Human carotid plaques with high CCS are richer in calcium and have lower amounts of glycosaminoglycan, parathyroid hormone, and tumor necrosis factor-α, which is one of the main proinflammatory cytokines involved in atherosclerosis. This suggests that CCS not only reflects the degree of calcification, but also other important biological components relevant for stability such as inflammation.
|
|
| 5. |
- Edsfeldt, Andreas, et al.
(author)
-
Soluble Urokinase Plasminogen Activator Receptor is Associated With Inflammation in the Vulnerable Human Atherosclerotic Plaque.
- 2012
-
In: Stroke: a journal of cerebral circulation. - 1524-4628. ; 43:12, s. 3305-3312
-
Journal article (peer-reviewed)abstract
- Recently, plasma soluble urokinase plasminogen activator receptor (suPAR) has gained interest as a marker of cardiovascular risk. suPAR is released through the cleavage of urokinase plasminogen activator receptor (uPAR), which is found in monocytes, activated T-lymphocytes and endothelial cells, all involved in atherosclerosis. suPAR levels have been well studied in plasma, but no studies have focused on suPAR in human atherosclerotic plaques. The aim of this study was to determine whether suPAR measured in the plaque is associated with symptomatic plaques and plaque inflammation.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Grönberg, Caitriona, et al.
(author)
-
Human Carotid Plaques With High Levels of Interleukin-16 Are Associated With Reduced Risk for Cardiovascular Events.
- 2015
-
In: Stroke: a journal of cerebral circulation. - 1524-4628. ; 46:10, s. 2748-2754
-
Journal article (peer-reviewed)abstract
- Interleukin-16 (IL-16) functions as a regulator of T-cell growth and acts as an inducer of cell migration. The aim of this study was to determine whether IL-16 measured in human carotid plaques was associated with symptoms (eg, stroke, transient ischemic attack, or amaurosis fugax), markers of plaque stability, and postoperative cardiovascular events.
|
|
| 9. |
- Hultman, Karin, et al.
(author)
-
Cartilage Oligomeric Matrix Protein Associates With a Vulnerable Plaque Phenotype in Human Atherosclerotic Plaques
- 2019
-
In: Stroke. - 1524-4628. ; 50:11, s. 3289-3292
-
Journal article (peer-reviewed)abstract
- Background and Purpose- Extracellular matrix proteins are important in atherosclerotic disease by influencing plaque stability and cellular behavior but also by regulating inflammation. COMP (cartilage oligomeric matrix protein) is present in healthy human arteries and expressed by smooth muscle cells. A recent study showed that transplantation of COMP-deficient bone marrow to apoE-/- mice increased atherosclerotic plaque formation, indicating a role for COMP also in bone marrow-derived cells. Despite the evidence of a role for COMP in murine atherosclerosis, knowledge is lacking about the role of COMP in human atherosclerotic disease. Methods- In the present study, we investigated if COMP was associated with a stable or a vulnerable human atherosclerotic plaque phenotype by analyzing 211 carotid plaques for COMP expression using immunohistochemistry. Results- Plaque area that stained positive for COMP was significantly larger in atherosclerotic plaques associated with symptoms (n=110) compared with asymptomatic plaques (n=101; 9.7% [4.7-14.3] versus 5.6% [2.8-9.8]; P=0.0002). COMP was positively associated with plaque lipids (r=0.32; P=0.000002) and CD68 cells (r=0.15; P=0.036) but was negatively associated with collagen (r=-0.16; P=0.024), elastin (r=-0.14; P=0.041), and smooth muscle cells (r=-0.25; P=0.0002). COMP was positively associated with CD163 (r=0.37; P=0.00000006), a scavenger receptor for hemoglobin/haptoglobin and a marker of Mhem macrophages, and with intraplaque hemorrhage, measured as glycophorin A staining (r=0.28; P=0.00006). Conclusions- The present study shows that COMP is associated to symptomatic carotid atherosclerosis, CD163-expressing cells, and a vulnerable atherosclerotic plaque phenotype in humans.
|
|
| 10. |
- Sun, Jiangming, et al.
(author)
-
Genetic Susceptibility to Mood Disorders and Risk of Stroke : A Polygenic Risk Score and Mendelian Randomization Study
- 2023
-
In: Stroke. - 1524-4628. ; 54:5, s. 1340-1346
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Mood disorders and strokes are often comorbid, and their health toll worldwide is huge. This study characterizes prognostic and causal roles of mood disorders in stroke.METHODS: We tested if genetic susceptibilities for mood disorders were associated with all strokes, ischemic strokes in the Malmö Diet and Cancer cohort (24 631 individuals with a median follow-up of 21.3 (interquartile range: 16.6-23.2) years. We further examined the causal effects for mood disorders on all strokes and ischemic strokes using summary statistics from large genome-wide association studies of mood disorders (up to 609 424 individuals, Psychiatric Genomics Consortium), all strokes and ischemic strokes (up to 446 696 individuals, MEGASTROKE Consortium).RESULTS: Among 24 366 stroke-free participants at baseline, 2632 individuals developed strokes, 2172 of them ischemic, during follow-up. After properly adjusting for well-known risk factors, participants in the highest quintile of polygenic risk scores for mood disorders had 1.45× (95% CI, 1.21-1.74) higher risk of strokes and 1.44× (95% CI, 1.18-1.76) higher risk of ischemic strokes compared with the lowest quintile in women. Mendelian randomization analyses suggested that mood disorders had a causal effect on strokes (odds ratio, 1.07 [95% CI, 1.03-1.11]) and ischemic strokes (odds ratio, 1.09 [95% CI, 1.04-1.13]).CONCLUSIONS: Our results suggest a causal role of mood disorders in the risk of stroke. High-risk women could be identified early in life using polygenic risk scores to ultimately prevent mood disorders and strokes.
|
|
