Hypercholesterolemia Impairs Transduction of Vasodilator Signals Derived From Ischemic Myocardium

Sato, Kouichi; Komaru, Tatsuya; Shioiri, Hiroki; Takeda, Satoru; Takahashi, Katsuaki; Kanatsuka, Hiroshi; Nakayama, Masaaki; Shirato, Kunio

doi:10.1161/01.atv.0000143387.58166.c0

Cited by 14 publications

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“…Several physiopathological and genetic situations can induce cardiac oxidative stress, such as hypercholesterolemia (Sato et al, 2004), mechanical stress in the myocardium (Aikawa et al, 2001) and inflammatory processes (Yao et al, 2006). Therefore, the marked cardiac inflammatory process in HL mice associated with oxidative stress due to the increased expression of CD40L in cardiac tissue and subsequently reduced bioavailability of nitric oxide (NO) hold the pathway of left ventricular hypertrophy observed in the HL mice in this study, characterized by the increase in collagen deposition and cardiomyocyte diameters.…”

Section: Discussionmentioning

confidence: 70%

Propolis and swimming in the prevention of atherogenesis and left ventricular hypertrophy in hypercholesterolemic mice

et al. 2015

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Aims: The present study verified the effect of propolis alone and its association with swimming in dyslipidemia, left ventricular hypertrophy and atherogenesis of hypercholesterolemic mice. Methods and Results: The experiments were performed in LDLr-/-mice, fed with high fat diet for 75 days, and were divided into four experimental groups (n=10): HL, sedentary, subjected to aquatic stress (5 min per day, 5 times per week); NAT submitted to a swimming protocol (1 hour per day, 5 times per week) from the 16 th day of the experiment; PRO, sedentary, submitted to aquatic stress and which received oral propolis extract (70 uL/animal/day) from the 16 th day of the experiment; HL+NAT+PRO, submitted to swimming and which received propolis as described above. After 75 days, blood was collected for analysis of serum lipids. The ratio between the ventricular weight (mg) and the animal weight (g) was calculated. Histological sections of the heart and aorta were processed immunohistochemically with anti-CD40L antibodies to evaluate the inflammatory process; stained with hematoxylin/eosin and picrosirius red to assess morphological and morphometric alterations. The HL animals showed severe dyslipidemia, atherogenesis and left ventricular hypertrophy, associated with a decrease in serum HDLc levels and subsequent development of cardiovascular inflammatory process, characterized by increased expression of CD40L in the left ventricle and aorta. Swimming and propolis alone and\or associated prevented the LVH, atherogenesis and arterial and ventricular inflammation, decreasing the CD40L expression and increasing the HDLc plasmatic levels. Conclusion: Propolis alone or associated with a regular physical activity is beneficial in cardiovascular protection through anti-inflammatory action.Keywords: dyslipidemia, left ventricular hypertrophy, propolis, LDLr-/-mice. Própolis e natação na prevenção da aterogênese e hipertrofia ventricular esquerda de camundongos hipercolesterolêmicos ResumoObjetivos: O presente estudo verificou o efeito do própolis associação ou não com a natação na dislipidemia, na hipertrofia ventricular esquerda e aterogênese de camundongos hipercolesterolêmicos. Métodos e Resultados: Os experimentos foram realizados em camundongos LDLr-/-, alimentados com dieta hiperlipídica por 75 dias, e divididos em quatro grupos experimentais (n = 10): HL, sedentários, foram submetidos ao estresse aquático (5 min por dia, cinco vezes por semana); NAT foram submetidos a um protocolo de natação (1 hora por dia, cinco vezes por semana) a partir do 16° dia do experimento; PRO, sedentários, submetidos a estresse aquático e que receberam extrato de própolis oral (70 uL / animal / dia) a partir do 16° dia do experimento; HL + NAC + PRO, submetidos a natação e que recebeu a própolis, como descrito acima. Após 75 dias, foi coletado sangue para análise do perfil lipídico. Calculou-se a relação entre o peso ventricular (mg) e o peso do animal (g). Os cortes histológicos do coração e aorta foram processados imunohistoquímicamente co...

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Section: Discussionmentioning

confidence: 70%

Propolis and swimming in the prevention of atherogenesis and left ventricular hypertrophy in hypercholesterolemic mice

et al. 2015

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“…Several physiopathological and genetic situations can induce cardiac oxidative stress, such as the increase in the concentration of AngII 31 , hypercholesteremia 32 , mechanical stress in the myocardium 33 and inflammatory processes 34 .…”

Section: Oxidative Stressmentioning

confidence: 99%

“…The hypercholesterolemia, in addition to inducing the oxidative stress 32 , can alter the function and expression of the K ATP channels in the myocardium 36 , inducing cardiac hypertrophy, simply due to the fact that the activation of these channels attenuates the cardiac hypertrophy through the inhibition of 70-KDa S6 Kinase 37 , an enzyme that acts as a trigger for protein synthesis in the myocardium remodeling.…”

Section: Hypercholesterolemiamentioning

confidence: 99%

Fatores e mecanismos envolvidos na hipertrofia ventricular esquerda e o papel anti-hipertrófico do óxido nítrico

Garcia¹,

Incerpi²

2008

Arq. Bras. Cardiol.

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SummaryThe left ventricular hypertrophy (LVH) occurs in response to the hemodynamic overload in some physiological and pathological conditions. However, it has not been completely elucidated whether the primary stimulation for the hypertrophy is the mechanical stretching of the heart, neurohumoral factors, or even the interaction of both. These factors are translated inside the cell as biochemical alterations that lead to the activation of second (cytosolic) and third (nuclear) messengers that will act in the cell nucleus, regulating transcription, and will finally determine the genic expression that induces LVH. The LVH is characterized by structural alterations due to the increase in the cardiomyocyte dimensions, the proliferation of the interstitial connective tissue and the rarefaction of the coronary microcirculation. Recently, nitric oxide (• NO) has appeared as an important regulator of cardiac remodeling, specifically recognized as an anti-hypertrophic mediator. Some studies have demonstrated the cellular targets, the anti-hypertrophic signaling pathways and the functional role of• NO. Thus, the LVH seems to develop as a result of the loss of the balance between the pro and the antihypertrophic signaling pathways. This new knowledge about the pro and anti-hypertrophic signaling pathways will allow the development of new strategies in the treatment of pathological LVH.

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“…Furthermore, H 2 O 2 potently dilates coronary arterial microvessels in endothelium-dependent and endothelium-independent fashion. 12 Accordingly, we hypothesized that H 2 O 2 derived from the beating heart mediates the dilation of the coronary microvessels during tachypacing.We tested the hypothesis using a bioassay method developed in our laboratory, [13][14][15] in which the isolated coronary vessel is placed on the beating heart, because the system enables us to separately control the beating heart and the coronary microvessels, and it is advantageous for detecting the myocardium-derived vasoactive signals. …”

mentioning

confidence: 99%

“…16 Beagle dogs of either gender (nϭ25; body weight, 5.8Ϯ0.2 kg; NARC, Chiba, Japan) were used and prepared as described in our previous studies. [13][14][15] Briefly, the dogs were anesthetized with ␣-chloralose (60 mg/kg, intravenous; Wako Pure Chemicals, Osaka, Japan) and artificially ventilated. The heart was exposed and paced at 120 bpm by left atrial pacing after the suppression of the sinoatrial node with formaldehyde injection.…”

mentioning

confidence: 99%

Hydrogen Peroxide Derived From Beating Heart Mediates Coronary Microvascular Dilation During Tachycardia

Kokusho

Komaru

Takeda

et al. 2007

ATVB

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Objective-Coronary flow is closely correlated to the myocardial metabolic demand. We tested the hypothesis that hydrogen peroxide (H 2 O 2 ) derived from beating hearts mediates metabolic coronary microvascular dilation. Methods and Results-We used a bioassay method in which an isolated microvessel is placed on a beating heart to detect myocardium-derived vasoactive mediators. A rabbit coronary arterial microvessel (detector vessel [DV], nϭ25) was pressurized and placed on a canine beating heart. After intrinsic tone of DV had developed, we observed DV at rest (heart rate, 120 bpm) and during tachypacing (heart rate, 240 bpm) using an intravital microscope equipped with a floating objective. The tachypacing produced DV dilation by 8.2% (PϽ0.01 versus baseline), and the dilation was abolished by cell-impermeable catalase (a H 2 O 2 scavenger, 500 U/mL). We performed myocardial biopsy at rest and tachypacing. The biopsy specimens were loaded with 2Ј,7Ј-dichlorodihydrofluorescein diacetate (10 mol/L) to visualize H 2 O 2, and observed with confocal microscopy. Dichlorofluorescein fluorescence was diffusely identified in the myocardium and the tachypacing increased the fluorescence intensity (PϽ0.01). Exogenous H 2 O 2 caused vasodilation of arterial microvessels in vitro in a concentration-dependent manner that was abolished by catalase. Conclusions-H 2 O 2 derived from the beating heart mediates tachypacing-induced metabolic coronary vasodilation in vivo.(Arterioscler Thromb Vasc Biol. 2007;27:1057-1063.)Key Words: coronary circulation Ⅲ myocardium Ⅲ reactive oxygen species Ⅲ tachycardia Ⅲ vasodilation C oronary blood flow is linearly correlated to the myocardial oxygen consumption. 1,2 The tight coupling between the cardiac metabolism and the flow conductance underlies the widely accepted assumption that the myocardium-derived vasoactive factor, so-called metabolic factor, rapidly regulates the vascular tone of coronary microvessels for matching the coronary flow to the cardiac metabolic state. However, the metabolic factor that is transmitted from the myocardium to the coronary microvessels has not been identified yet. Although there are many candidates for the mediators such as adenosine, prostanoids, autacoids, nitric oxide (NO), factors activating potassium channels, and so on, no substance solely explains the metabolic microvascular dilation. 3,4 Although excessive reactive oxygen species (ROS) are produced in various pathological conditions such as ischemia/reperfusion and cardiac failure 5,6 and are often hazardous for living organisms, increasing evidence has shown that ROS also play important roles as biological signals that mediate physiological phenomena at low concentrations. 7,8 In the field of vascular biology, hydrogen peroxide (H 2 O 2 ) has been known as one of the possible endothelium-derived hyperpolarizing factors. 9 The cardiac myocyte is another major source of ROS. 5,10 Superoxide (O 2 Ϫ ⅐ ) and H 2 O 2 are produced as byproducts of electron transfer reactions during normal aerobic meta...

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Hypercholesterolemia Impairs Transduction of Vasodilator Signals Derived From Ischemic Myocardium

Cited by 14 publications

References 50 publications

Propolis and swimming in the prevention of atherogenesis and left ventricular hypertrophy in hypercholesterolemic mice

Propolis and swimming in the prevention of atherogenesis and left ventricular hypertrophy in hypercholesterolemic mice

Fatores e mecanismos envolvidos na hipertrofia ventricular esquerda e o papel anti-hipertrófico do óxido nítrico

Hydrogen Peroxide Derived From Beating Heart Mediates Coronary Microvascular Dilation During Tachycardia

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