Cardiovascular protection by ezetimibe and influence on oxidative stress in mice exposed to intermittent hypoxia.

Ezetimibe is as an inhibitor of NPC1L1 protein, which has a key role in cholesterol absorption. The aim of this study was to evaluate the influence of ezetimibe on the plasma lipid profile, atherosclerotic lesions, and cardiomyocyte ultrastructure in an animal model of atherosclerosis with intermittent hypoxia. Apolipoprotein E-knockout mice received a high-fat diet for 30 days.

Comparison of the acute effects of right ventricular apical pacing and biventricular pacing in patients with heart failure.

Objective: Upgrading to biventricular (BiV) pacing benefits heart failure patients with right ventricular (RV) apical pacing. However, the impact of switching from RV apical pacing to BiV pacing on the left ventricular (LV) function accompanied by changes in the QRS duration remains unknown. We aimed to investigate the effects of BiV pacing in heart failure patients under RV apical pacing.

Atrial natriuretic peptide exerts protective action against angiotensin II-induced cardiac remodeling by attenuating inflammation via endothelin-1/endothelin receptor A cascade.

We aimed to investigate whether atrial natriuretic peptide (ANP) attenuates angiotensin II (Ang II)-induced myocardial remodeling and to clarify the possible molecular mechanisms involved. Thirty-five 8-week-old male Wistar-Kyoto rats were divided into control, Ang II, Ang II + ANP, and ANP groups. The Ang II and Ang II + ANP rats received 1 μg/kg/min Ang II for 14 days.

Molecular basis for clinical heterogeneity in inherited cardiomyopathies due to myopalladin mutations.

Abnormalities in Z-disc proteins cause hypertrophic (HCM), dilated (DCM) and/or restrictive cardiomyopathy (RCM), but disease-causing mechanisms are not fully understood. Myopalladin (MYPN) is a Z-disc protein expressed in striated muscle and functions as a structural, signaling and gene expression regulating molecule in response to muscle stress. MYPN was genetically screened in 900 patients with HCM, DCM and RCM, and disease-causing mechanisms were investigated using comparative immunohistochemical analysis of the patient myocardium and neonatal rat cardiomyocytes expressing mutant MYPN.

Sarcoidosis does not belong to or overlap with immunoglobulin G4-related diseases based on an assessment of serum immunoglobulin G4 levels in cardiac and noncardiac sarcoidosis.

Although sarcoidosis may exhibit histopathologic features similar to those of a newly emerging clinical entity, immunoglobulin G4-related sclerosing disease, sarcoidosis is currently not considered to be associated with immunoglobulin G4-related immunoinflammation. Not many studies on this association have been reported. We investigated serum immunoglobulin G4 levels among patients with sarcoidosis with or without cardiac involvement (cardiac sarcoidosis and non-cardiac sarcoidosis patients).

Effect of efonidipine on TGF-β1-induced cardiac fibrosis through Smad2-dependent pathway in rat cardiac fibroblasts.

Transforming growth factor beta-1 (TGF-β1) plays a critical role in progression of cardiac fibrosis, which may involve intracellular calcium change. We examined effects of efonidipine, a dual T-type and L-type calcium channel blocker (CCB), on TGF-β1-induced fibrotic changes in neonatal rat cardiac fibroblast. T-type and L-type calcium channel mRNAs were highly expressed in cultured cardiac fibroblasts.

Survival and changes in physical ability after coronary revascularization for octa-nonagenerian patients with acute coronary syndrome.

Elderly populations are increasingly represented among patients with acute coronary syndrome (ACS), and advanced age has been identified as an important risk factor for death and adverse outcome in patients with ACS treated invasively. Although considerable data have demonstrated a prognostic benefit of early revascularization in ACS particularly in high-risk patients, elderly patients with ACS are treated invasively less often than younger patients because older age is thought to be an independent predictor of mortality after percutaneous coronary intervention (PCI) in ACS. Over the past 5 years, a total of 54 ACS patients over 85 years old were treated.

Inhibitory effects of T/L-type calcium channel blockers on tubulointerstitial fibrosis in obstructed kidneys in rats.

Objectives: To examine the effect of L- and T/L-type calcium channel blockers on interstitial fibrosis in chronic unilateral ureteral obstruction (UUO). Tubulointerstitial fibrosis is a common outcome of several progressive renal diseases. Calcium channel blockers are widely used for the treatment of hypertension with renal diseases; however, the direct effect of calcium channel blockers on renal diseases independent of lowering blood pressure has not been fully elucidated.

Impact of outdoor temperature on prewaking morning surge and nocturnal decline in blood pressure in a Japanese population.

Seasonal variations in blood pressure (BP) have often been attributed to meteorological factors, especially changes in outdoor temperature. We evaluated the direct association between meteorological factors and circadian BP variability. Twenty-four-hour ambulatory BP was monitored continuously for 7 days in 158 subjects.

Enhanced expression of the ubiquitin-proteasome system in the myocardium from patients with dilated cardiomyopathy referred for left ventriculoplasty: an immunohistochemical study with special reference to oxidative stress.

The ubiquitin (Ub)-proteasome system (UPS) is an important proteolytic mechanism for selecting and digesting cytotoxic proteins. The aim of this study is to elucidate expression and in situ localization of the UPS in the myocardium from patients with dilated cardiomyopathy (DCM) with refractory heart failure. The expression profile of the oxidative stress-induced cytotoxic proteins was also examined.

Ca2+/calmodulin-dependent kinase IIdelta causes heart failure by accumulation of p53 in dilated cardiomyopathy.

Background: Dilated cardiomyopathy (DCM), characterized by dilatation and dysfunction of the left ventricle, is an important cause of heart failure. Many mutations in various genes, including cytoskeletal protein genes and contractile protein genes, have been identified in DCM patients, but the mechanisms of how such mutations lead to DCM remain unknown.

Methods And Results: We established the mouse model of DCM by expressing a mutated cardiac alpha-actin gene, which has been reported in patients with DCM, in the heart (mActin-Tg).

Effects of acarbose on the acceleration of postprandial hyperglycemia-induced pathological changes induced by intermittent hypoxia in lean mice.

Postprandial hyperglycemia (PPH) and intermittent hypoxia related to the sleep apnea syndrome are important predictors of cardiovascular disease. We investigated the effects of intermittent hypoxia on pathological changes in the left ventricular (LV) myocardium caused by PPH in lean mice and evaluated the influence of acarbose, an α-glucosidase inhibitor. Male C57BL/6J mice aged 8 weeks were exposed to intermittent hypoxia (8 h/day during the daytime) or kept under normoxia.

A sinus of Valsalva-right atrium fistula without aneurysm formation.

A 61-year-old man was admitted to the hospital because of orthopnea and was diagnosed with heart failure with a continuous heart murmur. A transthoracic echocardiogram revealed turbulent flow from the right coronary sinus of Valsalva to the right atrium throughout the cardiac cycle. Aortography confirmed the presence of a shunt jet from the right coronary sinus of Valsalva to the right atrium.

ATF6 is important under both pathological and physiological states in the heart.

Accumulation of unfolded proteins in the endoplasmic reticulum (ER) evokes the ER stress response, including activating transcription factor 6 (ATF6), a key transcriptional activator to maintain cellular homeostasis. The ER stress has recently been reported to cause various diseases, but the role of ATF6 in the heart remains unknown. We clarified the role of ATF6 in the heart.

Pitavastatin reduces oxidative stress and attenuates intermittent hypoxia-induced left ventricular remodeling in lean mice.

We have reported previously that intermittent hypoxia related to sleep apnea induces cardiovascular remodeling secondary to the oxidative stress. The aim of this study was to examine the effect of pitavastatin as an antioxidant to prevent intermittent hypoxia-induced left ventricular (LV) remodeling in mice without hypercholesterolemia. Eight-week-old male C57BL/6J mice (n=35) were exposed to intermittent hypoxia (30 s exposure to 5% oxygen, followed by 30 s exposure to 21% oxygen) for 8 h per day during the daytime or maintained under normoxic conditions; in addition, they were either treated with pitavastatin (3 mg kg(-1) per day) or vehicle for 10 days.

Enhanced expression of the S100A8/A9 complex in acute myocardial infarction patients.

Background: S100A8/A9 complex (S100A8/A9) is expressed in activated human neutrophils and macrophages. Enhanced expression of S100A8/A9 in atherosclerotic plaque of patients with unstable angina pectoris (UAP) has been demonstrated, but its profile in acute myocardial infarction (AMI) has not been clarified.

Methods And Results: Serum S100A8/A9 levels were serially measured in patients with AMI (n=55) and UAP (n=16) during the acute period.

Efficacy of olmesartan and nifedipine on recurrent hypoxia-induced left ventricular remodeling in diabetic mice.

Aims: Recurrent hypoxia due to sleep apnea syndrome is implicated in cardiovascular events, especially in diabetic patients, but the underlying mechanisms remain controversial. We previously reported that angiotensin II receptor blockers can improve hypoxia-induced left ventricular remodeling. The aim of this study was to examine the effect on left ventricular remodeling of adding a calcium channel blocker to angiotensin II receptor blocker therapy in diabetic mice exposed to recurrent hypoxia.

Usefulness of carvedilol to abolish myocardial postsystolic shortening in patients with idiopathic dilated cardiomyopathy.

Postsystolic shortening (PSS), a positive myocardial velocity after aortic valve closure as assessed by Doppler tissue imaging, is a common pathologic finding in patients with myocardial disease. Beta-blocker therapy can improve global and regional myocardial function. The aim of the present study was to examine whether the beta-blocker carvedilol might reduce the incidence and magnitude of PSS in patients with idiopathic dilated cardiomyopathy.

Dietary salt restriction activates mineralocorticoid receptor signaling in volume-overloaded heart failure.

Whether a high plasma aldosterone concentration induced by strict salt restriction promotes cardiac remodeling remains controversial. Male Sprague-Dawley rats at 10weeks of age were given normal salt (NS) (1.5% NaCl) or low salt (LS) (0.

Olmesartan ameliorates myocardial function independent of blood pressure control in patients with mild-to-moderate hypertension.

Angiotensin II receptor blockers (ARBs) are suggested to be protective against myocardial hypertrophy and fibrosis, although such beneficial effects remain to be elucidated in the human heart. The aim of the present study was to examine the effect of a novel ARB, olmesartan, on myocardial function of the left ventricle in patients with mildto-moderate hypertension. We investigated 10 patients (6 men and 4 women, 62 +/- 7 years of age) who were stable with a single regimen of amlodipine, which was switched to olmesartan.

Involvement of vascular angiotensin II-forming enzymes in the progression of aortic abdominal aneurysms in angiotensin II- infused ApoE-deficient mice.

Aim: Angiotensin (Ang) II-induced abdominal aortic aneurysm (AAA) in apoE-deficient mice has been used as a model of human AAA, but it has been unclear why the progression of AAA continues after stopping the Ang II infusion. The involvement of vascular Ang II-forming enzymes in the progression of AAA was studied.

Methods: ApoE-deficient mice were infused with Ang II (1,000 ng/kg/min) for 4 weeks and evaluated until 20 weeks after the Ang II infusion.

Chymase plays an important role in left ventricular remodeling induced by intermittent hypoxia in mice.

Intermittent hypoxia caused by sleep apnea is associated with cardiovascular disease. Chymase has been reported to play an important role in the development of cardiovascular disease, but it is unclear whether chymase is involved in the pathogenesis of left ventricular remodeling induced by intermittent hypoxia. The aim of this study was to evaluate the effect of a novel chymase inhibitor (NK3201) on hypoxia-induced left ventricular remodeling in mice.

High prevalence of chronic myocarditis in dilated cardiomyopathy referred for left ventriculoplasty: expression of tenascin C as a possible marker for inflammation.

The objectives of this study were to analyze the incidence of chronic myocarditis in dilated cardiomyopathy and to evaluate the diagnostic value of tenascin C for assessing inflammatory activity in the resected myocardium. Dilated cardiomyopathy patients with chronic myocarditis have a poor clinical outcome despite recent advances in medical treatments. Therefore, a precise diagnosis of inflammatory activity is critical to ensuring appropriate therapy.

Long-term angiotensin II blockade may improve not only hyperglycemia but also age-associated cardiac fibrosis.

In the present study, the effects of long-term angiotensin (Ang) II antagonism on the development of cardiac and endothelial disorders were examined in Spontaneously Diabetic Torii (SDT) rats. Blood glucose concentration started to increase markedly in the untreated SDT rats from 20 weeks of age, while the blood glucose concentrations of candesartan cilexetil-treated SDT rats were significantly lower until 30 weeks of age. Cardiac function deteriorated in SDT rats and was accompanied by severe cardiac fibrosis, cardiac hypertrophy, and microstructural pathologic change in cardiomyocytes.