Secoisolariciresinol diglucoside induces neovascularization-mediated cardioprotection against ischemia–reperfusion injury in hypercholesterolemic myocardium

Penumathsa, Suresh Varma; Koneru, Srikanth; Zhan, Lijun; John, Saji K; Menon, Venogopal P.; Prasad, Kailash; Maulik, Nilanjana

doi:10.1016/j.yjmcc.2007.09.014

Cited by 42 publications

(39 citation statements)

References 45 publications

(48 reference statements)

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“…These findings demonstrated that EMPs inhibited angiogenesis by inhibiting the eNOS pathway. A previous study demonstrated that eNOS expression was increased in hypercholesterolemia, which is consistent with our current findings that eNOS expression was slightly increased in LDLr Ϫ/Ϫ mice fed a Western diet for 2 wk (8,33,34). Our data showing that eNOS expression was decreased in hypercholesterolemic hearts when EMPs were present indicated that endothelial cells were quite harmful under such conditions and did not respond to exogenous angiogenic agents.…”

Section: Discussionsupporting

confidence: 92%

Endothelium-derived microparticles inhibit angiogenesis in the heart and enhance the inhibitory effects of hypercholesterolemia on angiogenesis

Chang

Luo

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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YQ, Ou JS. Endothelium-derived microparticles inhibit angiogenesis in the heart and enhance the inhibitory effects of hypercholesterolemia on angiogenesis. Am J Physiol Endocrinol Metab 300: E661-E668, 2011. First published January 18, 2011; doi:10.1152/ajpendo.00611.2010.-Therapeutic angiogenesis remains unsuccessful in coronary artery disease. It is known that plasma endothelium-derived microparticles (EMPs) are increased in coronary artery disease and that hypercholesterolemia can inhibit angiogenesis. We evaluated the relationship between EMPs and hypercholesterolemia in the impairment of angiogenesis. EMPs isolated from human umbilical vein endothelial cells were injected into low-density lipoprotein receptor-null (LDLr Ϫ/Ϫ ) mice fed a Western diet for 2 wk and C57BL6 mice for 6 h or were directly added to the tissue culture media. Hearts isolated from mice were sectioned and cultured, and endothelial tube formation was measured. The expression and phosphorylation of endothelial NO synthase (eNOS) and the generation of NO in the hearts were determined. Angiogenesis was inhibited by pathophysiological concentrations of EMPs but not physiological concentrations of EMPs in hearts from C57BL6 mice. However, angiogenesis was inhibited by EMPs at both physiological and pathophysiological concentrations of EMPs in hearts from hypercholesterolemic LDLr Ϫ/Ϫ mice. Pathophysiological concentrations of EMPs decreased eNOS phosphorylation at Ser 1177 and NO generation without altering eNOS expression in hearts from C57BL6 mice. Both physiological and pathophysiological concentrations of EMPs decreased not only eNOS phosphorylation at Ser 1177 and NO generation, but eNOS expression in hypercholesterolemic hearts from LDLr Ϫ/Ϫ mice. These data demonstrated that pathophysiological concentrations of EMPs could inhibit angiogenesis in hearts by decreasing eNOS activity. EMPs and hypercholesterolemia mutually enhanced their inhibitory effect of angiogenesis by inducing eNOS dysfunction. Our findings suggest a novel mechanism by which hypercholesterolemia impairs angiogenesis. cardiovascular diseases; endothelial nitric oxide synthase; nitric oxide ENDOTHELIUM-DERIVED MICROPARTICLES (EMPs) are subcellular fragments of the endothelial cell lipid bilayer (7,39). EMPs are present at relatively low concentrations under normal physiological conditions and, upon activation, are released from endothelial cells (6,7,26,39). Elevated plasma concentrations of EMPs have been reported in many cardiovascular diseases, such as coronary artery disease (20,30,51), acute coronary syndrome (2,3,25), and hypertension (16,29,36,48). Indeed, an increase in the concentration of EMPs has been suggested as a marker of endothelial dysfunction (15).Angiogenesis has been identified as a potential therapy for myocardial ischemia due to coronary artery disease. Many studies in animal models have successfully increased angiogenesis in the heart (13, 38, 43). However, clinical trials have failed to demonstrate that therapeutic angiogenesis is as effective ...

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Section: Discussionsupporting

confidence: 92%

Endothelium-derived microparticles inhibit angiogenesis in the heart and enhance the inhibitory effects of hypercholesterolemia on angiogenesis

Chang

Luo

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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“…76 SDG (20 mg/kg body wt/d for 8 weeks) reduced serum levels of TC, TG, and LDL-C by 33%, 39%, and 45%, respectively, and raised HDL-C levels by 22% in hypercholesterolemic rats. 77 …”

Section: Secoisolariciresinol Diglucosidementioning

confidence: 99%

Flaxseed and Cardiovascular Health

Prasad

2009

Journal of Cardiovascular Pharmacology

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156

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Flaxseed and its components may improve cardiovascular health because of their numerous attributes. Flaxseed contains 35% of its mass as oil, of which 55% is alpha-linolenic acid (ALA). Flax meal, which is devoid of oil, contains the lignan secoisolariciresinol diglucoside (SDG). Flaxseed, flaxseed with very low ALA, flaxseed oil, flax lignan complex (FLC), and SDG reduce the development of hypercholesterolemic atherosclerosis by 46%, 69%, 0%, 73%, and 34%, respectively, in the rabbit model. FLC and SDG slow the progression of atherosclerosis but have no effect in regression of atherosclerosis. Suppression of atherosclerosis by flaxseed is the result of its lignan content and not the result of ALA content. Suppression of atherosclerosis is associated with lowering of serum lipids and antioxidant activity. Effects of flaxseed on serum lipids in experimental animals are variable from no change to slight reduction. Flaxseed oil does not affect serum lipids, except for a slight reduction in serum triglycerides. Lignan in general reduces serum total cholesterol and low-density lipoprotein cholesterol and raises serum high-density lipoprotein cholesterol. SDG and its metabolites have antioxidant activity. Flaxseed and flaxseed oil do not have antioxidant activity except they suppress oxygen radical production by white blood cells. Flaxseed oil/ALA has variable effects on inflammatory mediators/markers (interleukin [IL]-1beta, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor-alpha, interferon-gamma, C-reactive protein, and serum amyloid A). Doses of ALA less than 14 g/d do not affect inflammatory mediators/markers, but 14 g/d or greater reduce inflammatory mediators/markers. Flaxseed oil decreases soluble vascular cell adhesion molecule-1 but has no effect on soluble intracellular adhesion molecule-1, soluble E-selectin, and monocyte colony-stimulating factor. Flaxseed has variable effects on IL-6, high-sensitivity C-reactive protein, and soluble vascular cell adhesion molecule-1. FLC reduces plasma levels of C-reactive protein but has no effects on IL-6, tumor necrosis factor-alpha, soluble intracellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, or monocyte chemoattractant protein. Flaxseed has a very small hypotensive effect, but flaxseed oil does not lower blood pressure. However, SDG is a very potent hypotensive agent. Flaxseed oil decreases platelet aggregation and increases platelet activating inhibitor-1 and bleeding time. Flaxseed and FLC have no effect on the hemopoietic system. SDG is a potent angiogenic and antiapoptotic agent that may have a role in cardioprotection in ischemic heart disease. In conclusion, flaxseed, FLC, and SDG, but not flaxseed oil, suppress atherosclerosis, and FLC and SDG slow progression of atherosclerosis but have no effect on regression. Flaxseed oil suppresses oxygen radical production by white blood cells, prolongs bleeding time, and in higher doses suppresses serum levels of inflammatory mediators and does not lower serum lipids.

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“…Thus, hypercholesterolemic animals are more likely to experience disruption in COXIII activity; however, the specific effects shown in Figure 7 will need further analysis in order to place them in a mechanistic picture of hypercholesterolemic disruption of mitochondrial function. The lack of significant differences in the VEGF content of heart tissue from any of the groups of rabbits included in the present study is puzzling given the adverse effect on neovascularization of hypercholesterolemia observed in rats and the pivotal role played by VEGF in this process (Figure 7b) [28]. The outcome of these studies also merits further exploration in future research.…”

Section: Resultsmentioning

confidence: 82%

“…The design of these experiments was guided by an intriguing observation by other investigators that a pro-angiogenic drug called secoisolariciresinol diglucoside significantly protects against ischemia-reperfusion injury to hearts in a diet-induced hypercholesterolemic rat model by reduction of oxidative stress, accompanied by decreased infarct size of isolated hearts, increased HO-1 expression and significant increases in FS and EF [28]. This precedent underscores the importance of FS, EF and parameters for the assessment of the severity of hypercholesterolemia-associated cardiac insufficiency and therapeutic management of this and related cardiac disorders.…”

Section: Resultsmentioning

confidence: 99%

Adverse Impact of Diet-Induced Hypercholesterolemia on Cardiovascular Tissue Homeostasis in a Rabbit Model: Time-Dependent Changes in Cardiac Parameters

Kertész

Bombicz

Priksz

et al. 2013

IJMS

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The present study evaluates a hypothesis that diet-related hypercholesterolemia increases oxidative stress-related burden to cardiovascular tissue, resulting in progressively increased mortality, along with deterioration of electrophysiological and enzymatic function in rabbit myocardium. New Zealand white rabbits were divided into four groups, defined as follows: GROUP I, cholesterol-free rabbit chow for 12 weeks; GROUP II, cholesterol-free chow, 40 weeks; GROUP III, chow supplemented with 2% cholesterol, 12 weeks; GROUP IV, chow supplemented with 2% cholesterol, 40 weeks. At the 12 and 40 weeks time points, animals in each of the aforementioned cohorts were subjected to echocardiographic measurements, followed by sacrifice. Significant deterioration in major outcome variables measured in the present study were observed only in animals maintained for 40 weeks on 2% cholesterol-supplemented chow, with much lesser adverse effects noted in animals fed high cholesterol diets for only 12 weeks. It was observed that rabbits receiving high cholesterol diets for 40 weeks exhibited significantly increased mortality, worsened ejection fraction and general deterioration of cardiac functions, along with increased atherosclerotic plaque formation and infarct size. Additionally, myocardium of GROUP IV animals was observed to contain lower levels of heme oxygenase-1 (HO-1) and cytochrome c oxidase III (COX III) protein relative to the controls.

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Secoisolariciresinol diglucoside induces neovascularization-mediated cardioprotection against ischemia–reperfusion injury in hypercholesterolemic myocardium

Cited by 42 publications

References 45 publications

Endothelium-derived microparticles inhibit angiogenesis in the heart and enhance the inhibitory effects of hypercholesterolemia on angiogenesis

Endothelium-derived microparticles inhibit angiogenesis in the heart and enhance the inhibitory effects of hypercholesterolemia on angiogenesis

Flaxseed and Cardiovascular Health

Adverse Impact of Diet-Induced Hypercholesterolemia on Cardiovascular Tissue Homeostasis in a Rabbit Model: Time-Dependent Changes in Cardiac Parameters

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