Atherosclerosis

Libby, Peter; Buring, Julie E.; Badimon, Lina; Hansson, Göran K.; Deanfield, John; Bittencourt, Márcio Sommer; Tokgözoğlu, Lâle; Lewis, Eldrin F.

doi:10.1038/s41572-019-0106-z

Cited by 1,722 publications

(1,258 citation statements)

References 165 publications

Supporting

Mentioning

1,216

Contrasting

Unclassified

Order By: Relevance

“…Nevertheless, there were higher BMI values in the intermediate group and a not significant tendency towards higher BMI values in inflammatory SSc as compared to non-inflammatory SSc. Inflammation is a known risk factor for atherosclerosis [28]. Accordingly, we found a trend towards a higher prevalence of atherosclerosis and coronary artery disease in the intermediate group and in inflammatory SSc.…”

Section: Discussionmentioning

confidence: 46%

Inflammatory stays inflammatory: a subgroup of systemic sclerosis characterized by high morbidity and inflammatory resistance to cyclophosphamide

et al. 2019

View full text Add to dashboard Cite

Background/purpose: Elevated levels of C-reactive protein (CRP) in systemic sclerosis (SSc) have been linked to early inflammatory stages of the disease. This study has been designed to investigate CRP levels longitudinally in a cohort of SSc patients and to correlate these findings with comorbidities and disease characteristics. Methods: In this retrospective study, patients with SSc treated at the outpatient clinic of the Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, were analyzed. Only patients with at least three consecutive visits and at least 1 year follow-up were included in this study. CRP serum levels were measured at every visit and categorized as positive if CRP concentrations were ≥ 5 mg/l. Subjects with elevated CRP levels at more than 80% of visits were defined as inflammatory SSc. The longitudinal CRP profiles were correlated with disease characteristics and comorbidities. Results: A total of 1815 consecutive visits of 131 SSc patients were analyzed. Over the observed time span (7.6 (1.0-19.5) years), 18.3% (n = 24) of patients had continuously elevated CRP levels (inflammatory SSc), whereas in 29% (n = 38), CRP levels were always in the normal range. There was no association between disease duration and CRP levels at first visit. Inflammatory SSc was associated with male gender (p = 0.022), anti-Scl-70 antibodies (p = 0.009), diffuse cutaneous SSc (p = 0.036), pulmonary fibrosis (p < 0.001), rheumatoid arthritis (p = 0.007), and cardiac arrhythmia (p = 0.048). Moreover, patients with inflammatory SSc revealed higher modified Rodnan skin scores (p < 0.001); lower forced vital capacity (FVC) (p < 0.001), total lung capacity (p = 0.001), and diffusing capacity (p = 0.008); and faster decline of FVC per year (p = 0.007). Even treatment with cyclophosphamide (CYC) did not decrease CRP levels (p = 0.754). Conclusion: Inflammatory SSc is characterized by a more severe phenotype, high morbidity, and a large proportion of male patients. Even treatment with CYC does not alter CRP levels in this subpopulation with a high unmet medical need.

show abstract

Section: Discussionmentioning

confidence: 46%

Inflammatory stays inflammatory: a subgroup of systemic sclerosis characterized by high morbidity and inflammatory resistance to cyclophosphamide

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Atherosclerosis refers to the accumulation of fibrofatty material in the intima layer of the arteries, characterized by chronic inflammation and excessive cell proliferation [56]. It is the most common underlying pathology of coronary artery disease, peripheral artery disease, and cerebrovascular disease [57].…”

Section: Tweak and Atherosclerosismentioning

confidence: 99%

Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (TWEAK)/Fibroblast Growth Factor-Inducible 14 (Fn14) Axis in Cardiovascular Diseases: Progress and Challenges

Gutiérrez-Muñoz

Blázquez-Serra

Martı́n-Ventura

et al. 2020

Cells

View full text Add to dashboard Cite

Cardiovascular diseases (CVD) are the leading cause of mortality in Western countries. CVD include several pathologies, such as coronary artery disease, stroke, peripheral artery disease, and aortic aneurysm, among others. All of them are characterized by a pathological vascular remodeling in which inflammation plays a key role. Interaction between different members of the tumor necrosis factor superfamily and their cognate receptors induce several biological actions that may participate in CVD. The cytokine tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its functional receptor, fibroblast growth factor-inducible 14 (Fn14), are abundantly expressed during pathological cardiovascular remodeling. The TWEAK/Fn14 axis controls a variety of cellular functions, such as proliferation, differentiation, and apoptosis, and has several biological functions, such as inflammation and fibrosis that are linked to CVD. It has been demonstrated that persistent TWEAK/Fn14 activation is involved in both vessel and heart remodeling associated with acute and chronic CVD. In this review, we summarized the role of the TWEAK/Fn14 axis during pathological cardiovascular remodeling, highlighting the cellular components and the signaling pathways that are involved in these processes.

show abstract

“…According to current understanding, the initial stages of atherosclerosis development are dependent on two processes: accumulation of intracellular lipids (mainly cholesterol and its esters) and the inflammatory response of the resident arterial cells accompanied by the recruitment of circulating inflammatory cells into the subendothelial space of arterial intima where they differentiate into macrophages of the vascular wall [33]. We have previously shown that lipid accumulation within the arterial cells is the trigger that initiates the activation of cellular functions associated with atherogenesis [34].…”

Section: Discussionmentioning

confidence: 99%

Signaling Pathways Potentially Responsible for Foam Cell Formation: Cholesterol Accumulation or Inflammatory Response—What is First?

Orekhov

Sukhorukov

Nikiforov

et al. 2020

IJMS

View full text Add to dashboard Cite

Accumulation of lipid-laden (foam) cells in the arterial wall is known to be the earliest step in the pathogenesis of atherosclerosis. There is almost no doubt that atherogenic modified low-density lipoproteins (LDL) are the main sources of accumulating lipids in foam cells. Atherogenic modified LDL are taken up by arterial cells, such as macrophages, pericytes, and smooth muscle cells in an unregulated manner bypassing the LDL receptor. The present study was conducted to reveal possible common mechanisms in the interaction of macrophages with associates of modified LDL and non-lipid latex particles of a similar size. To determine regulatory pathways that are potentially responsible for cholesterol accumulation in human macrophages after the exposure to naturally occurring atherogenic or artificially modified LDL, we used transcriptome analysis. Previous studies of our Int.Int. J. Mol. Sci. 2020, 21, 2716 2 of 17 group demonstrated that any type of LDL modification facilitates the self-association of lipoprotein particles. The size of such self-associates hinders their interaction with a specific LDL receptor. As a result, self-associates are taken up by nonspecific phagocytosis bypassing the LDL receptor. That is why we used latex beads as a stimulator of macrophage phagocytotic activity. We revealed at least 12 signaling pathways that were regulated by the interaction of macrophages with the multiple-modified atherogenic naturally occurring LDL and with latex beads in a similar manner. Therefore, modified LDL was shown to stimulate phagocytosis through the upregulation of certain genes. We have identified at least three genes (F2RL1, EIF2AK3, and IL15) encoding inflammatory molecules and associated with signaling pathways that were upregulated in response to the interaction of modified LDL with macrophages. Knockdown of two of these genes, EIF2AK3 and IL15, completely suppressed cholesterol accumulation in macrophages. Correspondingly, the upregulation of EIF2AK3 and IL15 promoted cholesterol accumulation. These data confirmed our hypothesis of the following chain of events in atherosclerosis: LDL particles undergo atherogenic modification; this is accompanied by the formation of self-associates; large LDL associates stimulate phagocytosis; as a result of phagocytosis stimulation, pro-inflammatory molecules are secreted; these molecules cause or at least contribute to the accumulation of intracellular cholesterol. This chain of events may explain the relationship between cholesterol accumulation and inflammation. The primary sequence of events in this chain is related to inflammatory response rather than cholesterol accumulation.

show abstract

Atherosclerosis

Cited by 1,722 publications

References 165 publications

Inflammatory stays inflammatory: a subgroup of systemic sclerosis characterized by high morbidity and inflammatory resistance to cyclophosphamide

Inflammatory stays inflammatory: a subgroup of systemic sclerosis characterized by high morbidity and inflammatory resistance to cyclophosphamide

Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (TWEAK)/Fibroblast Growth Factor-Inducible 14 (Fn14) Axis in Cardiovascular Diseases: Progress and Challenges

Signaling Pathways Potentially Responsible for Foam Cell Formation: Cholesterol Accumulation or Inflammatory Response—What is First?

Contact Info

Product

Resources

About