Remnant Lipoproteins and Atherogenesis

Kawakami, Akio; Yoshida, Masayuki

doi:10.5551/jat.12.73

Cited by 45 publications

(25 citation statements)

References 34 publications

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“…According to Ando et al [6], a decreased Angptl3 expression was associated with reduced plasma TG-rich lipoproteins and suppressed atherosclerosis in apolipoprotein E knockout mice. Atherogenicity of TG-rich lipoproteins or atherogenic lipoprotein changes in high TG state are also known in humans [18, 19]. Therefore, the observed positive association between plasma ANGPTL3 and CA-IMT and FA-IMT may be mediated by lipid changes.…”

Section: Discussionmentioning

confidence: 97%

Association between Plasma Angiopoietin-Like Protein 3 and Arterial Wall Thickness in Healthy Subjects

et al. 2006

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Background: Angiopoietin-like protein 3 (ANGPTL3) is a liver-derived plasma protein that modulates plasma triglyceride clearance, angiogenesis and atherosclerosis in experimental models. So far, no study has examined its role in atherosclerosis in human subjects. We evaluated the possible association between plasma ANGPTL3 level and carotid artery intima-media thickness (CA-IMT) and femoral artery intima-media thickness (FA-IMT) in healthy human subjects. Methods: The subjects were 381 healthy volunteers. Plasma ANGPTL3 was determined by a specific ELISA. CA-IMT and FA-IMT were measured by high-resolution B-mode ultrasonography. Results: The plasma ANGPTL3 level was 764 ± 291 ng/ml (mean ± SD). CA-IMT showed a significant positive correlation with plasma ANGPTL3 and other classical risk factors such as age, blood pressure, and plasma glucose and lipid levels. The positive association between ANGPTL3 and CA-IMT remained significant after adjustment for age, sex, smoking, body mass index, systolic blood pressure, plasma glucose, insulin resistance index, triglyceride, and high-density and low-density lipoprotein cholesterol levels. ANGPTL3 also showed a positive association with FA-IMT independent of these factors. Conclusions: These results demonstrate for the first time that ANGPTL3 is closely associated with arterial wall thickness in human subjects.

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Section: Discussionmentioning

confidence: 97%

Association between Plasma Angiopoietin-Like Protein 3 and Arterial Wall Thickness in Healthy Subjects

et al. 2006

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“…It is also established that plasma levels of RLP significantly and independently correlate with decreased endothelium-dependent vasomotor function and that they decrease endothelium-dependent vasodilation in isolated rabbit aorta (53). It is suggested that endothelial dysfunction results from the elevated oxidative stress, and that RLP elevates expression of Rho-kinase in smooth muscle cells as well (6).…”

Section: Triglyceride-rich Lipoproteinsmentioning

confidence: 98%

“…Numerous clinical and epidemiological studies revealed that increased serum triglyceride levels are closely related to atherosclerosis, independently of serum levels of HDL and LDL (11,53).…”

Section: Triglyceride-rich Lipoproteinsmentioning

confidence: 99%

“…In cell culture, RLP increase monocyte adhesion in vascular EC most probably by the mechanism of RhoA activation, which belong to the family of small GTP-binding proteins, via the protein kinase C (PKC), resulting in activation of focal adhesion kinase (FAK) and beta-1-integrin (53). Besides, RLP induce proliferation of smooth muscle cells via epidermal growth factor (EGF) receptor transactivation, and heparin-binding EGF-like growth factor (HB-EGF) shedding (57).…”

Section: Triglyceride-rich Lipoproteinsmentioning

confidence: 99%

“…It has recently been established that RLP produced by hydrolysis of TRL in the state of hypertriglyceridaemia and during the postprandial period can be considered atherogenic and independent coronary risk factors, rivalling LDL, particularly with respect to the metabolic syndrome. They involve series of particles that are heterogenous with respect to their size, density and lipid/apo composition (6,53).…”

Section: Triglyceride-rich Lipoproteinsmentioning

confidence: 99%

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Lipids and atherosclerosis

Djeric¹,

Stokić²,

Vučković³

et al. 2006

Jugoslav Med Biohem

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Lipids play a pivotal role in the atherogenesis, starting from initial changes. Their predictive value in coronary heart disease and development of novel therapeutic strategies is an increasingly addressed issue nowadays. LDL particles are fundamental, because reduction of LDL-cholesterol was proven to reduce morbidity and mortality associated with atherosclerosis. Besides the regulation of LDL-receptor expression, significant clinical importance is assigned to oxidized LDL (ox-LDL) and small dense LDL (sdLDL) that are generated through intravascular remodelling of triglyceride-rich lipoproteins, while the exact role of anti-oxLDL antibodies in atherosclerosis propagation and their clinical significance still remain unclear. In recent years, however, better understanding of the basic mechanisms involved in atherosclerosis development, as well as in the metabolic fate of lipids and lipoproteins, emphasizes the crucial role of other lipoprotein particles not only in the propagation, but also in the initiation of atherosclerosis and atherothrombosis.

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Remnant Lipoprotein Cholesterol and Mortality After Acute Myocardial Infarction: Further Evidence for a Hypercholesterolemia Paradox From the TRIUMPH Registry

Martin¹,

Faridi²,

Joshi³

et al. 2015

Clinical Cardiology

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Background Remnants are partially-hydrolyzed, triglyceride-rich lipoproteins that, like other apolipoprotein B-containing lipoproteins, are atherogenic. Prior observational studies suggest paradoxically better outcomes in hypercholesterolemic patients who sustain an acute myocardial infarction (AMI), one of several known recurrent risk paradoxes. To date, the association of directly-measured remnant lipoprotein cholesterol (RLP-C) with survival has not been examined after an AMI. Methods We examined 2,465 AMI survivors in TRIUMPH, a prospective, 24-center US study of AMI outcomes. Lipoprotein cholesterol subfractions were directly measured by ultracentrifugation. RLP-C was defined as IDL-C+VLDL3-C. Given a linear relationship between RLP-C and mortality, we examined RLP-C by tertiles and continuously. Cox regression hazard ratios were adjusted for the GRACE score and 23 other co-variates. Results Participants were 58±12 years old (mean±SD) and 68% were men. After 2 years of follow-up, 226 (9%) participants died. The mortality proportion was 12.4% in the lowest tertile of RLP-C (0–15 mg/dL), 8.5% in the middle tertile (16–23 mg/dL), and 6.8% in the highest tertile (24–120 mg/dL) (p<0.001). A one SD increase in RLP-C (11 mg/dL) predicted a 24% lower adjusted risk of 2-year mortality (HR, 0.76; 95% CI 0.64–0.91). Similar results were found for a one SD increase in IDL-C (HR per 8 mg/dL, 0.80; 0.67–0.96), VLDL3-C (HR per 4 mg/dL, 0.74; 0.61–0.89), and VLDL-C (HR per 8 mg/dL, 0.69; 0.55–0.85). Conclusion In conclusion, higher RLP-C levels were associated with lower mortality 2 years after AMI despite rigorous adjustment for known confounders. Unknown protective factors, or a lead-time bias, likely explain the paradox.

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Remnant Lipoproteins and Atherogenesis

Cited by 45 publications

References 34 publications

Association between Plasma Angiopoietin-Like Protein 3 and Arterial Wall Thickness in Healthy Subjects

Association between Plasma Angiopoietin-Like Protein 3 and Arterial Wall Thickness in Healthy Subjects

Lipids and atherosclerosis

Remnant Lipoprotein Cholesterol and Mortality After Acute Myocardial Infarction: Further Evidence for a Hypercholesterolemia Paradox From the TRIUMPH Registry

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