Relationship Between Cytokine Levels and Coronary Artery Disease in Women

Batuman, Olcay; Go, Darlene; Clark, Luther T.; Smith, Eric L.; Clements, Peggy; Feit, Alan; Lederer, David J.

doi:10.1097/00132580-200103000-00004

Cited by 14 publications

(14 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This assay is sensitive to all 3 isoforms of TGF-␤; therefore, to specifically quantitate total TGF-␤2 in hypoxic and nonhypoxic supernatants, aliquots of the identical supernatants used in MLEC assay were acid-activated and subjected to enzyme-linked immunosorbent assay (ELISA) (Quantikine, R&D Systems) as previously described. 37 Results (not shown) confirmed that TGF-␤2 levels were increased by 2-fold in hypoxic supernatants. Because measurement of bioactive TGF-␤s by ELISA is not yet reliably accomplished by existing commercial kits, this assay can only confirm the increase in total TGF-␤2 determined by the MLEC assay.…”

Section: Tgf-␤ Assaymentioning

confidence: 74%

Response to hypoxia involves transforming growth factor-β2 and Smad proteins in human endothelial cells

Akman

Zhang

Siddiqui

et al. 2001

Blood

Self Cite

View full text Add to dashboard Cite

Oxygen deprivation (hypoxia) is a consistent component of ischemia that induces an inflammatory and prothrombotic response in the endothelium. In this report, it is demonstrated that exposure of endothelial cells to hypoxia (1% O 2 ) increases messenger RNA and protein levels of transforming growth factor-␤2 (TGF-␤2), a cytokine with potent regulatory effects on vascular inflammatory responses. Messenger RNA levels of the TGF-␤2 type II membrane receptor, which is a serine threonine kinase, also increased. The stimulatory effect of hypoxia was found to occur at the level of transcription of the TGF-␤2 gene and involves Smad proteins, a class of intracellular signaling proteins that mediates the downstream effects of TGF-␤ receptors. Transient transfection studies showed that the region spanning ؊77 and ؊40 base pairs within the TGF-␤2 promoter (harboring a Smad-binding "CAGA box") is activated in hypoxic cells compared with nonhypoxic controls (P < .01). Hypoxia also stimulated transcription from another promoter, 3TP-Lux, a reporter construct responsive to Smads and TGF-␤. In addition, specific binding to a Smad-binding oligonucleotide was observed with nuclear extracts from hypoxic endothelial cells but not from nonhypoxic cells. It is concluded that Smad proteins, which can regulate endothelial responses to mechanical and inflammatory stress, also may play an important role in vascular responses to hypoxia and ischemia. IntroductionOne of the earliest responses of endothelium to hypoxia is inflammation, and the balance between positive and negative regulators of this inflammatory response is a determinant of endothelial adaptation to hypoxia. Proinflammatory endothelial responses induced by hypoxia involve production of cytokines, chemokines, 1-3 tissue factor, 4 and plasminogen activator inhibitor-1 (PAI-1). 5 Recent studies indicate that activation of the transcription factor early growth response-1 (Egr-1) by hypoxia is responsible for the procoagulant profile and vascular remodeling that ultimately result in the tissue damage associated with ischemia. 4 Adaptive responses to hypoxia are also regulated at a transcriptional level, which is best exemplified by activation of the transacting protein hypoxia-inducible factor-1 (HIF-1), which stimulates differential expression of specific genes and results in increases in glucose uptake, glycolytic enzyme production, and angiogenesis. 6,7 The transforming growth factor-␤ (TGF-␤) family of growth factors has an especially critical role in modulation of vascular inflammatory responses and remodeling, [8][9][10] and up-regulation of TGF-␤ production is an invariant response to vascular injury, indicating that regulation of gene expression of the TGF-␤ proteins by quiescent and injured endothelium is likely to be a critical factor affecting the course of vascular inflammation. This hypothesis is supported by demonstration of defective vasculogenesis and increased and ultimately lethal vascular inflammation in mice null for TGF-␤s, 11,12 their membrane receptors, 13...

show abstract

Section: Tgf-␤ Assaymentioning

confidence: 74%

Response to hypoxia involves transforming growth factor-β2 and Smad proteins in human endothelial cells

Akman

Zhang

Siddiqui

et al. 2001

Blood

Self Cite

View full text Add to dashboard Cite

show abstract

“…It is possible that the relevance of TGF-β1 in discriminating CAD could only be observed in severe disease, as shown by other authors in CAD [13,25,26] and peripheral artery disease [27]. Using clinical criteria for the diagnosis of significant atherosclerotic vascular disease in hemodialysis patients, Stefoni et al showed reduced survival in a 24 month follow-up of patients with lower TGF-β1 levels at the beginning of the study [25].…”

Section: Discussionmentioning

confidence: 99%

'Correction:' Serum transforming growth factor beta-1 (TGF-beta-1) levels in diabetic patients are not associated with pre-existent coronary artery disease

Schaan¹,

Quadros²,

Sarmento‐Leite³

et al. 2007

Cardiovasc Diabetol

View full text Add to dashboard Cite

Background: The association between TGF-β1 levels and long-term major adverse cardiovascular events (MACE) in patients with coronary artery disease (CAD) is controversial. No study specifically addressed patients with CAD and diabetes mellitus (DM). The association between TGF-β1 levels and long-term major adverse cardiovascular events (MACE) in patients with coronary artery disease (CAD) is controversial. No study specifically addressed patients with CAD and diabetes mellitus (DM).

show abstract

“…Nonetheless, we propose that these relationships warrant further empirical evaluation given our current findings, as well as other lines of evidence which implicate persistent sleep disruption and depression as contributors to chronic low-grade inflammation (6, 39, 51-57). Low-grade chronic inflammation is a risk factor for various adverse health outcomes including cardiovascular disease, metabolic syndrome (51, 58-63) depression(64), sleep apnea (65-68), polycystic ovarian syndrome (PCOS) (69, 70), and obesity (69, 71, 72). The cytokine levels we observed were similar to these other studies that have reported on chronic low-grade inflammation.…”

Section: Discussionmentioning

confidence: 99%

Disturbed Sleep and Inflammatory Cytokines in Depressed and Nondepressed Pregnant Women

Okun

Luther

Wisniewski

et al. 2013

Psychosomatic Medicine

View full text Add to dashboard Cite

Objective Disturbed sleep and depression are potential risk factors for pregnancy complications. Both conditions are noted to dysregulate biological pathways responsible for maintaining homeostatic balance and pregnancy health. Depression during pregnancy is associated with poor sleep. Thus, we explored whether disturbed sleep was associated with inflammatory cytokines and risk for adverse pregnancy outcomes, as well as whether depression augmented the sleep-cytokine relationship thereby additively contributing to risk for adverse outcomes. Methods Interview-assessed sleep and plasma cytokine concentrations were evaluated in a cohort of depressed and non-depressed pregnant women (N= 168) at 20 and 30 weeks gestation. Outcomes evaluated included preterm birth, birth weight, and peripartum events. Results Among depressed women, short sleep duration (< 7 hours) was associated with higher IL-8 across time (β=.506, p = .001), poor sleep efficiency (< 85%) was associated with higher IL-6 (β=.205, p = .006), and daytime naps were associated with higher TNF-α (β=.105, p =.024). Aspects of poor sleep were associated with having a lower weight baby (ps < 053). Among depressed women, IFN-γ increased risk for preterm birth (OR = 1.175, p = .032). Trends for IL-6 and higher birth weight (β = 105.2, p = .085); IFN-γ and lower birth weight (β = −19.92, p < .069); and increased IL-8 and babies weighing < 4000g, (OR =.72, p < .083) were observed. Conclusions Although speculative, disturbed sleep may disrupt normal immune processes and contribute to adverse pregnancy outcomes. Exploratory analyses indicate depression modifies these relationships.

show abstract

Relationship Between Cytokine Levels and Coronary Artery Disease in Women

Cited by 14 publications

References 36 publications

Response to hypoxia involves transforming growth factor-β2 and Smad proteins in human endothelial cells

Response to hypoxia involves transforming growth factor-β2 and Smad proteins in human endothelial cells

'Correction:' Serum transforming growth factor beta-1 (TGF-beta-1) levels in diabetic patients are not associated with pre-existent coronary artery disease

Disturbed Sleep and Inflammatory Cytokines in Depressed and Nondepressed Pregnant Women

Contact Info

Product

Resources

About