Tomatoes, lysophosphatidic acid, and the small intestine: new pieces in the puzzle of apolipoprotein mimetic peptides?

High-Density Lipoprotein

“…The recent work of Navab et al 112,113 is consistent with this hypothesis. They found that feeding LDL receptor null mice a high-fat, high-cholesterol Western diet increased unsaturated (but not saturated) lysophosphatidic acid levels in the small intestine and caused changes in small intestine gene expression.…”

Tg6F ameliorates the increase in oxidized phospholipids in the jejunum of mice fed unsaturated LysoPC or WD

“…We successfully expressed the 6F peptide in transgenic tomatoes and demonstrated that adding 2.2% by weight of freezedried transgenic tomato powder expressing the 6F peptide to WD ameliorated dyslipidemia and systemic inflammation in LDLR-null mice (17,18). We also demonstrated that this dose of the freeze-dried tomato powder containing the 6F peptide ameliorated aortic atherosclerosis that was induced by either adding unsaturated LPA to standard mouse chow, or by feeding WD to LDLR-null mice (8,9).…”

“…The recognition of oxidized phospholipids in the artery wall was established by using antibodies to oxidized phospholipids (5) and confirmed by our laboratory using MS (6). Oxidized phospholipids have been implicated in both pro-inflammatory and anti-inflammatory processes acting through multiple signaling pathways (7).We previously reported that adding 1 g of unsaturated (but not saturated) lysophosphatidic acid (LPA) to each gram of standard mouse chow induced dyslipidemia and systemic inflammation in LDL receptor (LDLR)-null mice similar to that seen when the mice were fed a Western diet (WD) (8,9). More recently, we demonstrated that the LPA-mediated dyslipidemia resulted in aortic atherosclerosis in LDLR-null mice that was similar in cellular characteristics to that seen on feeding these mice WD (10).…”

“…We previously reported that adding 1 g of unsaturated (but not saturated) lysophosphatidic acid (LPA) to each gram of standard mouse chow induced dyslipidemia and systemic inflammation in LDL receptor (LDLR)-null mice similar to that seen when the mice were fed a Western diet (WD) (8,9). More recently, we demonstrated that the LPA-mediated dyslipidemia resulted in aortic atherosclerosis in LDLR-null mice that was similar in cellular characteristics to that seen on feeding these mice WD (10).…”

Source and role of intestinally derived lysophosphatidic acid in dyslipidemia and atherosclerosis

“…Remarkably, the tissue content of unsaturated LPA in the small intestine signifi cantly correlated with the extent of aortic atherosclerosis ( 11 ). LPA is emerging as an important signaling molecule in diverse biological processes and disease states , and its role in the pathogenesis of atherosclerosis has been emphasized in recent years (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40).…”