Vascular calcification in patients with large-vessel vasculitis compared to patients with hyperlipidemia

Guan

et al. 2022

ATVB

Background: Endothelial cells (ECs) play a critical role in angiogenesis and vascular remodeling. The heterogeneity of ECs has been reported at adult stages, yet it has not been fully investigated. This study aims to assess the transcriptional heterogeneity of developmental ECs at spatiotemporal level and to reveal the changes of embryonic ECs clustering when endothelium-enriched microRNA-126 (miR-126) was specifically knocked out. Methods: C57BL/6J mice embryos at day 14.5 were harvested and digested, followed by fluorescence-activated cell sorting to enrich ECs. Then, single-cell RNA sequencing was applied to enriched embryonic ECs. Tie2 (Tek receptor tyrosine kinase)-cre–mediated ECs-specific miR-126 knockout mice were constructed, and ECs from Tie2-cre–mediated ECs-specific miR-126 knockout embryos were subjected to single-cell RNA sequencing. Results: Embryonic ECs were clustered into 11 groups corresponding to anatomic characteristics. The vascular bed (arteries, capillaries, veins, lymphatics) exhibited transcriptomic similarity across the developmental stage. Embryonic ECs had higher proliferative potential than adult ECs. Integrating analysis showed that 3 ECs populations (hepatic, mesenchymal transition, and pulmonary ECs) were apparently disorganized after miR-126 being knocked out. Gene ontology analysis revealed that disrupted ECs were mainly related to hypoxia, glycometabolism, and vascular calcification. Additionally, in vivo experiment showed that Tie2-cre–mediated ECs-specific miR-126 knockout mice exhibited excessive intussusceptive angiogenesis; reductive glucose and pyruvate tolerance; and excessive accumulation of calcium. Agonist miR-126-3p agomir significantly rescued the phenotype of glucose metabolic dysfunction in Tie2-cre–mediated ECs-specific miR-126 knockout mice. Conclusions: The heterogeneity of ECs is established as early as the embryonic stage. The deficiency of miR-126 disrupts the differentiation and diversification of embryonic ECs, suggesting that miR-126 plays an essential role in the maintenance of ECs heterogeneity.

Section: Resultsmentioning

confidence: 99%

Single-Cell Transcriptome Analysis Reveals Embryonic Endothelial Heterogeneity at Spatiotemporal Level and Multifunctions of MicroRNA-126 in Mice

Guan

et al. 2022

ATVB

Therapeutic Advances in Musculoskeletal

“… 19 , 21 – 24 Moreover, calcifications can be found in atheromatous plaques as in old inflammatory lesions too. 25 , 26 …”

Section: Discussionmentioning

confidence: 99%

Risk factors for symptomatic vascular events in giant cell arteritis: a study of 254 patients with large-vessel imaging at diagnosis

Mornac

Agard

Hardouin

et al. 2021

Aims: To identify factors associated with vascular events in patients with giant cell arteritis (GCA). Methods: We performed a retrospective study of GCA patients diagnosed over a 20-year-period, who all underwent vascular imaging evaluation at diagnosis. Symptomatic vascular events were defined as the occurrence of any aortic event (aortic dissection or symptomatic aortic aneurysm), stroke, myocardial infarction, limb or mesenteric ischemia and de novo lower limbs arteritis stage 3 or 4. Patients with symptomatic vascular event (VE+) and without were compared, and risk factors were identified in a multivariable analysis. Results: Thirty-nine (15.4%) of the 254 included patients experienced at least one symptomatic vascular event during follow-up, with a median time of 21.5 months. Arterial hypertension, diabetes, lower limbs arteritis or vascular complication at diagnosis were more frequent in VE+ patients ( p < 0.05), as an abnormal computed tomography (CT)-scan at diagnosis ( p = 0.04), aortitis ( p = 0.01), particularly of the descending thoracic aorta ( p = 0.03) and atheroma ( p = 0.03). Deaths were more frequent in the VE+ group (37.1 versus 10.3%, p = 0.0003). In multivariable analysis, aortic surgery [hazard ratio (HR): 10.46 (1.41–77.80), p = 0.02], stroke [HR: 22.32 (3.69–135.05), p < 0.001], upper limb ischemia [HR: 20.27 (2.05–200.12), p = 0.01], lower limb ischemia [HR: 76.57 (2.89–2027.69), p = 0.009], aortic atheroma [HR: 3.06 (1.06–8.82), p = 0.04] and aortitis of the descending thoracic aorta on CT-scan at diagnosis [HR: 4.64 (1.56–13.75), p = 0.006] were independent predictive factors of a vascular event. Conclusion: In this study on GCA cases with large vessels imaging at diagnosis, aortic surgery, stroke, upper or lower limb ischemia, aortic atheroma and aortitis of the descending thoracic aorta on CT-scan, at GCA diagnosis, were independent predictive factors of a vascular event. Plain language summary Risk factors for symptomatic vascular events in giant cell arteritis This study was performed to identify the risk factors for developing symptomatic vascular event during giant cell arteritis (GCA) because these are poorly known. We performed a retrospective study of GCA patients diagnosed over a 20-year-period, who all underwent vascular imaging evaluation at diagnosis. Patients with symptomatic vascular event (VE+) and without (VE-) were compared, and risk factors were identified in a multivariable analysis. Thirty-nine patients experienced at least one symptomatic vascular event during follow-up, with a median time of 21.5 months. Arterial hypertension, diabetes, lower limbs arteritis or vascular complication at diagnosis were significantly more frequent in VE+ patients, as an abnormal CT-scan at diagnosis, aortitis, particularly of the descending thoracic aorta and atheroma. Deaths were more frequent in the VE+ group. Among 254 GCA patients, 39 experienced at least one vascular event during follow-up. Aortic surgery, stroke, upper and lower limb ischemia were vascular event risk factors. Aortic atheroma and descending thoracic aorta aortitis on CT-scan were vascular event risk factors. This study on GCA cases with large vessels imaging at diagnosis, showed that aortic surgery, stroke, upper or lower limb ischemia, aortic atheroma and aortitis of the descending thoracic aorta on CT-scan, at GCA diagnosis, were independent predictive factors of a vascular event.

“…But inflammation is not the only mechanism of TA patients involving coronary artery disease. Previous studies have shown that vascular calcification in TA is not only related to inflammation but also related to age and the use of glucocorticoids (7). Glucocorticoid therapy has a complex relationship with the development of atherosclerosis.…”

Section: The Multivariate Analysis Of the Risk Factors Of Ta Involvin...mentioning

confidence: 96%

“…Poland showed that the incidence of TA was estimated to be 0.92/1 million per year. TA mostly occurs in young women and the proportion of men and women in different groups around the world is different, mostly 1 (5)(6)(7)(8)(9)(10)(11). The age of onset is mainly 5-40-years-old, the peak is 20-30-years-old, and there is a main peak between 15-19-years-old in female patients (11,12).…”

Section: Hscpr Esr Biochemical Indexes and Cardiac Functionmentioning

confidence: 99%

“…With the increase of age, the late coronary stenosis may be caused by the contraction of the inflammatory tissue and calcium deposition. There are also studies that show that vascular calcification is not only related to inflammation but also to age and the use of glucocorticoids (7). It has been found that LP (a) in TA patients is significantly increased (8).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A study on the risk factors of coronary artery disease in patients with Takayasu arteritis

Wang¹,

Jia²,

Zhou³

et al. 2020

J Thorac Dis

Background:The aim of this study was to investigate the risk factors of Takayasu arteritis (TA) involving the coronary artery.Methods: Patients with TA involving coronary artery were included in this study. According to the patients' condition of coronary artery involvement, they were divided into two groups: group A: TA involved coronary artery disease [at least one coronary artery stenosis (≥50%)] and group B: TA did not involve coronary artery. A logistic regression model was used to analyze the risk factors of arteritis involving the patients' coronary artery lesions.Results: A total of 442 TA patients were included in this study. The patients were significantly older in group A than those patients in group B (52.54±11.17 vs. 37.73±12.72, P<0.001). The age of onset in group A was significantly older than those patients in group B (42.21±11.46 vs. 32.74±13.13, P<0.001). The patients in group A had a longer course of disease (P<0.001), larger BMI (P=0.002) and higher rates of smoking, drinking, diabetes, dyslipidemia (P<0.05) when compared with group B. The level of eGFR was significantly decreased and the UA and TG levels were significantly increased in group A when compared with group B(P<0.05). Besides, the risk factors for TA involving coronary artery included the age of TA onset (OR =1.143, 95% CI: 1.007-1.298, P=0.039), course of TA (OR =1.165, 95% CI: 1.025-1.324, P=0.020), and BMI (OR =1.100, 95% CI: 1.021-1.185, P=0.013). Conclusions:The later the age of TA onset, the longer the course of TA onset and the more traditional risk factors associated with atherosclerosis, the more vulnerable patients are to coronary artery involvement and this may not be related to clinical disease activity.