Cholesterol Effects on Endoglin and Its Downstream Pathways in ApoE/LDLR Double Knockout Mice

Strasky, Zbynek; Vecerova, Lenka; Rathouska, Jana; Slanarova, M.; Brčáková, Eva; Kudlackova, Zdenka; Andrýs, Ctirad; Mičuda, Stanislav; Nachtigal, Petr

doi:10.1253/circj.cj-10-1285

Cited by 21 publications

(16 citation statements)

References 49 publications

(39 reference statements)

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“…In apolipoprotein E/LDL receptor knockout mice, hyperlipidemia was shown to cause increased blood sEng level and enhanced atherosclerosis with decreased endoglin expression, 11 and atorvastatin treatment resulted in LDL cholesterol reduction and decreased sEng levels and decreased atherosclerotic lesions with increased endoglin expression.…”

Section: Discussionmentioning

confidence: 98%

“…3 Increased sEng levels in blood and enhanced atherosclerosis with decreased endoglin expression were demonstrated in apolipoprotein E/low-density lipoprotein (LDL) receptor knockout mice fed by cholesterol-rich diet. 11 Increased sEng levels may result in reduced TGF-β signaling, leading to enhanced atherosclerosis. However, blood sEng levels in patients with atherosclerotic diseases, such as coronary artery disease (CAD), remain controversial.…”

Section: See Accompanying Editorial On Page 10mentioning

confidence: 99%

“…In apolipoprotein E/LDL receptor knockout mice, hyperlipidemia caused increased sEng levels and enhanced atherosclerosis with decreased endoglin expression. 11 In human coronary atherosclerotic plaques, increased endoglin expression was reported. 7,8 Therefore, we also speculate that patients with CAD may have decreased blood sEng levels and increased endoglin expression of coronary atherosclerotic plaques.…”

Section: Saita Et Al Soluble Endoglin Levels In Cad 51mentioning

confidence: 99%

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Plasma Soluble Endoglin Levels Are Inversely Associated With the Severity of Coronary Atherosclerosis—Brief Report

Saita

Miura

Suzuki-Sugihara

et al. 2017

ATVB

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Objective-Transforming growth factor-β inhibits migration and proliferation of endothelial and smooth muscle cells.Endoglin is a transmembrane receptor for transforming growth factor-β1 and transforming growth factor-β3. Endoglin is released into blood as a soluble form (soluble endoglin [sEng]), but plasma sEng levels in patients with coronary artery disease (CAD) have not been elucidated. Approach and Results-We measured plasma sEng levels in 244 patients undergoing coronary angiography. The severity of coronary atherosclerosis was evaluated as the numbers of >50% stenotic vessels and segments. CAD was found in 147 patients, of whom 55 had 1-vessel, 42 had 2-vessel, and 50 had 3-vessel disease. Compared with 97 patients without CAD, 147 with CAD had lower sEng levels (median 4.04 versus 4.37 ng/mL; P<0.005). A stepwise decrease in sEng levels was found based on the number of stenotic vessels: 4.37 in CAD(−), 4.23 in 1-vessel, 4.13 in 2-vessel, and 3.74 ng/mL in 3-vessel disease (P<0.005). sEng levels inversely correlated with the number of stenotic segments (r=−0.25; P<0.001). In multivariate analysis, sEng was an independent factor for 3-vessel disease and CAD. Odds ratios for CAD and 3-vessel disease were 0.97 (95% confidence interval, 0.95-0.99; P<0.02) and 0.96 (95% confidence interval, 0.93-0.99; P<0.01) for a 0.1 ng/mL increase in sEng levels, respectively. Conclusions-Plasma sEng levels were low in patients with CAD, especially 3-vessel disease, and were inversely associated with the severity of coronary atherosclerosis. The study sponsors had no role in the design, analysis, and interpretation of the study. The online-only Data Supplement is available with this article at http://atvb.ahajournals.org/lookup/suppl

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Section: Discussionmentioning

confidence: 98%

Section: See Accompanying Editorial On Page 10mentioning

confidence: 99%

Section: Saita Et Al Soluble Endoglin Levels In Cad 51mentioning

confidence: 99%

See 1 more Smart Citation

Plasma Soluble Endoglin Levels Are Inversely Associated With the Severity of Coronary Atherosclerosis—Brief Report

Saita

Miura

Suzuki-Sugihara

et al. 2017

ATVB

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“…A soluble form of endoglin (sEng) is released from membrane bound Eng by proteolytic cleavage of its extracellular domain during endothelial injury or inflammation and subsequently sEng enters the blood circulation [5,6]. Increased levels of sEng in plasma have been detected in patients with cardiovascular-related disorders like atherosclerosis [7,8],…”

Section: Introductionmentioning

confidence: 99%

Soluble endoglin and hypercholesterolemia aggravate endothelial and vessel wall dysfunction in mouse aorta

et al. 2018

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“…Increased levels of circulating sEng have been found in various cardiovascular system-related pathological conditions like preeclampsia [4], hypertension, diabetes mellitus [6], atherosclerosis [7,8] and hypercholesterolemia [9]. We proposed that high levels of sEng may be considered as a biomarker related to the endothelial dysfunction [2].…”

Section: Introductionmentioning

confidence: 99%

High Levels of Soluble Endoglin Induce a Proinflammatory and Oxidative-Stress Phenotype Associated with Preserved NO-Dependent Vasodilatation in Aortas from Mice Fed a High-Fat Diet

et al. 2016

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Aims: A soluble form of endoglin (sEng) was proposed to participate in the induction of endothelial dysfunction in small blood vessels. Here, we tested the hypothesis that high levels of sEng combined with a high-fat diet induce endothelial dysfunction in an atherosclerosis-prone aorta. Methods and Results: Six-month-old female and male transgenic mice overexpressing human sEng (Sol-Eng⁺) with low (Sol-Eng⁺low) or high (Sol-Eng⁺high) levels of plasma sEng were fed a high-fat rodent diet containing 1.25% cholesterol and 40% fat for 3 months. The plasma cholesterol and mouse sEng levels did not differ in the Sol-Eng⁺high and Sol-Eng⁺low mice. The expression of proinflammatory (P-selectin, ICAM-1, pNFκB and COX-2) and oxidative-stress-related markers (HO-1, NOX-1 and NOX-2) in the aortas of Sol-Eng⁺high female mice was significantly higher than in Sol-Eng⁺low female mice. Endothelium-dependent vasodilatation induced by acetylcholine was preserved better in the Sol-Eng⁺high female mice than in the Sol-Eng⁺low female mice. Conclusion: These results suggest that high concentrations of sEng in plasma in combination with a high-fat diet induce the simultaneous activation of proinflammatory, pro-oxidative and vasoprotective mechanisms in mice aorta and the balance of these biological processes determines whether the final endothelial phenotype is adaptive or maladaptive.

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Cholesterol Effects on Endoglin and Its Downstream Pathways in ApoE/LDLR Double Knockout Mice

Cited by 21 publications

References 49 publications

Plasma Soluble Endoglin Levels Are Inversely Associated With the Severity of Coronary Atherosclerosis—Brief Report

Plasma Soluble Endoglin Levels Are Inversely Associated With the Severity of Coronary Atherosclerosis—Brief Report

Soluble endoglin and hypercholesterolemia aggravate endothelial and vessel wall dysfunction in mouse aorta

High Levels of Soluble Endoglin Induce a Proinflammatory and Oxidative-Stress Phenotype Associated with Preserved NO-Dependent Vasodilatation in Aortas from Mice Fed a High-Fat Diet

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