Why and how increased plasma ceramides predict future cardiovascular events?

Öörni, Katariina; Jauhiainen, Matti; Kovanen, Petri T.

doi:10.1016/j.atherosclerosis.2020.09.030

Cited by 9 publications

(9 citation statements)

References 22 publications

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“…Elevated levels of ceramides have also been reported in the blood plasma of patients with hypertension, insulin resistance, or type 2 diabetes mellitus [50][51][52]. Therefore, it may be suggested that monitoring the blood plasma ceramide levels may help to predict pathological events or disease development [53][54][55]. It should be noted that the set of significant CER species identified in our study includes ceramides with odd carbon chain.…”

Section: Discussionmentioning

confidence: 56%

Changes in Phospholipid/Ceramide Profiles and Eicosanoid Levels in the Plasma of Rats Irradiated with UV Rays and Treated Topically with Cannabidiol

Łuczaj

Jastrząb

Domingues

et al. 2021

IJMS

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Chronic UV radiation causes oxidative stress and inflammation of skin and blood cells. Therefore, in this study, we assessed the effects of cannabidiol (CBD), a natural phytocannabinoid with antioxidant and anti-inflammatory properties, on the phospholipid (PL) and ceramide (CER) profiles in the plasma of nude rats irradiated with UVA/UVB and treated topically with CBD. The results obtained showed that UVA/UVB radiation increased the levels of phosphatidylcholines, lysophospholipids, and eicosanoids (PGE2, TxB2), while downregulation of sphingomyelins led to an increase in CER[NS] and CER[NDS]. Topical application of CBD to the skin of control rats significantly upregulated plasma ether-linked phosphatidylethanolamines (PEo) and ceramides. However, CBD administered to rats irradiated with UVA/UVB promoted further upregulation of CER and PEo and led to significant downregulation of lysophospholipids. This was accompanied by the anti-inflammatory effect of CBD, manifested by a reduction in the levels of proinflammatory PGE2 and TxB2 and a dramatic increase in the level of anti-inflammatory LPXA4. It can therefore be suggested that topical application of CBD to the skin of rats exposed to UVA/UVB radiation prevents changes in plasma phospholipid profile resulting in a reduction of inflammation by reducing the level of LPE and LPC species and increasing antioxidant capacity due to upregulation of PEo species.

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Section: Discussionmentioning

confidence: 56%

Changes in Phospholipid/Ceramide Profiles and Eicosanoid Levels in the Plasma of Rats Irradiated with UV Rays and Treated Topically with Cannabidiol

Łuczaj

Jastrząb

Domingues

et al. 2021

IJMS

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“…also found a plasmatic depletion of long-chain Cer 24:1, which is synthetized by a specific Cer2 Synthase and has been previously reported to represent the major Cer species involved in defective angiogenesis [56]. Moreover, a low concentration of very-long-chain Cers has been reported to be related to increased cardiovascular risk [57]. The evidence that a depletion of very-long chain Cer 24:1 in MA associates with the increase of S1P and DHS1P, the most abundant sphingoid bases in plasma (see targeted analysis reported in Figure 4), may reflect a release of pro-angiogenic and cell growth-inducing lipid biomarkers from the newly produced MA vessels.…”

Section: Discussionmentioning

confidence: 64%

Plasma Lipid Profiling Contributes to Untangle the Complexity of Moyamoya Arteriopathy

Dei

Carrozzini

Pollaci

et al. 2021

IJMS

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Moyamoya arteriopathy (MA) is a rare cerebrovascular disorder characterized by ischemic/hemorrhagic strokes. The pathophysiology is unknown. A deregulation of vasculogenic/angiogenic/inflammatory pathways has been hypothesized as a possible pathophysiological mechanism. Since lipids are implicated in modulating neo-vascularization/angiogenesis and inflammation, their deregulation is potentially involved in MA. Our aim is to evaluate angiogenic/vasculogenic/inflammatory proteins and lipid profile in plasma of MA patients and control subjects (healthy donors HD or subjects with atherosclerotic cerebrovascular disease ACVD). Angiogenic and inflammatory protein levels were measured by ELISA and a complete lipidomic analysis was performed on plasma by mass spectrometry. ELISA showed a significant decrease for MMP-9 released in plasma of MA. The untargeted lipidomic analysis showed a cumulative depletion of lipid asset in plasma of MA as compared to HD. Specifically, a decrease in membrane complex glycosphingolipids peripherally circulating in MA plasma with respect to HD was observed, likely suggestive of cerebral cellular recruitment. The quantitative targeted approach demonstrated an increase in free sphingoid bases, likely associated with a deregulated angiogenesis. Our findings indicate that lipid signature could play a central role in MA and that a detailed biomarker profile may contribute to untangle the complex, and still obscure, pathogenesis of MA.

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“… 28 Similarly, increased concentrations of plasma ceramides predict cardiovascular deaths. 29 , 30 Since a large proportion of plasma sphingolipids are carried by LDL particles, their increased plasma concentrations largely reflect their content in LDL particles.…”

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confidence: 99%

Overfeeding Saturated Fat Increases LDL (Low-Density Lipoprotein) Aggregation Susceptibility While Overfeeding Unsaturated Fat Decreases Proteoglycan-Binding of Lipoproteins

Ruuth

Lahelma

Luukkonen

et al. 2021

ATVB

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Objective: We recently showed that measurement of the susceptibility of LDL (low-density lipoprotein) to aggregation is an independent predictor of cardiovascular events. We now wished to compare effects of overfeeding different dietary macronutrients on LDL aggregation, proteoglycan-binding of plasma lipoproteins, and on the concentration of oxidized LDL in plasma, 3 in vitro parameters consistent with increased atherogenicity. Approach and Results: The participants (36 subjects; age, 48±10 years; body mass index, 30.9±6.2 kg/m 2 ) were randomized to consume an extra 1000 kcal/day of either unsaturated fat, saturated fat, or simple sugars (CARB) for 3 weeks. We measured plasma proatherogenic properties (susceptibility of LDL to aggregation, proteoglycan-binding, oxidized LDL) and concentrations and composition of plasma lipoproteins using nuclear magnetic resonance spectroscopy, and in LDL using liquid chromatography mass spectrometry, before and after the overfeeding diets. LDL aggregation increased in the saturated fat but not the other groups. This change was associated with increased sphingolipid and saturated triacylglycerols in LDL and in plasma and reduction of clusterin on LDL particles. Proteoglycan binding of plasma lipoproteins decreased in the unsaturated fat group relative to the baseline diet. Lipoprotein properties remained unchanged in the CARB group. Conclusions: The type of fat during 3 weeks of overfeeding is an important determinant of the characteristics and functional properties of plasma lipoproteins in humans. REGISTRATION: URL: http://www.clinicaltrials.gov ; Unique identifier NCT02133144.

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Why and how increased plasma ceramides predict future cardiovascular events?

Cited by 9 publications

References 22 publications

Changes in Phospholipid/Ceramide Profiles and Eicosanoid Levels in the Plasma of Rats Irradiated with UV Rays and Treated Topically with Cannabidiol

Changes in Phospholipid/Ceramide Profiles and Eicosanoid Levels in the Plasma of Rats Irradiated with UV Rays and Treated Topically with Cannabidiol

Plasma Lipid Profiling Contributes to Untangle the Complexity of Moyamoya Arteriopathy

Overfeeding Saturated Fat Increases LDL (Low-Density Lipoprotein) Aggregation Susceptibility While Overfeeding Unsaturated Fat Decreases Proteoglycan-Binding of Lipoproteins

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