Eicosapentaenoic Acid Preserves Mitochondrial Quality and Attenuates Cardiac Remodeling After Myocardial Infarction in Rats.

Eicosapentaenoic acid (EPA) reduces the risk of ischemic heart diseases and is a component of mitochondria. We herein investigated whether dietary EPA mediated mitochondrial fatty acid compositions, dynamics, and functions, resulting in the attenuation of cardiac remodeling after myocardial infarction (MI). The coronary artery of male rats was ligated to induce MI, and they were then treated with or without EPA (1000 mg/kg/day) for 12 weeks.

Roles of autophagy in angiotensin II-induced cardiomyocyte apoptosis.

Autophagy is a self-degradation process of cytoplasmic components and occurs in the failing heart. Angiotensin II plays a critical role in the progression of heart failure and induces autophagy. We investigated the mechanism underlying angiotensin II-enhanced autophagy and examined the role of autophagy in angiotensin II-induced cardiomyocyte injury.

Nicorandil Suppresses Ischemia-Induced Norepinephrine Release and Ventricular Arrhythmias in Hypertrophic Hearts.

Purpose: Ventricular arrhythmias (VAs) are a common cause of sudden death in acute myocardial infarction (MI), for which hypertension is a major risk factor. Nicorandil opens ATP-sensitive potassium (KATP) channels, which are expressed by nerve terminals and cardiomyocytes and regulate the release of norepinephrine (NE). However, the effects of nicorandil on ischemic NE release in cardiac tissue remain unclear.

Angelica acutiloba Exerts Antihypertensive Effect and Improves Insulin Resistance in Spontaneously Hypertensive Rats Fed with a High-Fat Diet.

Introduction: Angelica acutiloba is one of the crude drugs used in Chinese herbal medicine, and its intake is expected to improve metabolic syndrome-associated disorders. Here, we examined the effects of A. acutiloba extract (AAE) on hypertension and insulin resistance induced by the treatment of high-fat diet (HFD) to spontaneously hypertensive rats (SHRs).

A Glucagon-like Peptide 1 Analog Protects Mitochondria and Attenuates Hypoxia-Reoxygenation Injury in Cultured Cardiomyocytes.

Glucagon-like peptide 1 (GLP-1) analogs improve glycemic control in diabetes and protect the heart against ischemia-reperfusion injury. However, the mechanisms underlying this protection remain unclear. Mitochondria are essential for myocyte homeostasis.

Secreted protein acidic and rich in cysteine (SPARC) and a disintegrin and metalloproteinase with thrombospondin type 1 motif (ADAMTS1) increments by the renin-angiotensin system induce renal fibrosis in deoxycorticosterone acetate-salt hypertensive rats.

Secreted protein acidic and rich in cysteine (SPARC), an extracellular matrix (ECM) protein, was recently shown to induce collagen deposition through the production of a disintegrin and metalloproteinase with thrombospondin type 1 motif (ADAMTS1) in the aging heart. ADAMTS1 regulates ECM turnover by degrading ECM components, and its excessive activation contributes to various pathological states, including fibrosis. The present study investigated the pathophysiological regulation and role of SPARC and ADAMTS1 in renal fibrosis using uninephrectomized rats treated with deoxycorticosterone acetate (DOCA, 40 mg/kg/week, subcutaneously) and salt (1% in drinking water).

Induction of autophagy has protective roles in imatinib-induced cardiotoxicity.

Cardiotoxicity is one of the severe adverse effects of chemotherapeutic agents. Imatinib was previously reported to induce cardiotoxicity. Autophagy is an intracellular bulk protein and organelle degradation process, but its roles in cardiac diseases are unclear.

Febuxostat Attenuates the Progression of Periodontitis in Rats.

Introduction: Periodontitis is a lifestyle-related disease that is characterized by chronic inflammation in gingival tissue. Febuxostat, a xanthine oxidase inhibitor, exerts anti-inflammatory and antioxidant effects.

Objective: The present study investigated the effects of febuxostat on periodontitis in a rat model.

Preconditioning with Short-term Dietary Restriction Attenuates Cardiac Oxidative Stress and Hypertrophy Induced by Chronic Pressure Overload.

Left ventricular (LV) hypertrophy and associated heart failure are becoming a more prevalent and critical public health issue with the aging of society, and are exacerbated by reactive oxygen species (ROS). Dietary restriction (DR) markedly inhibits senescent changes; however, prolonged DR is difficult. We herein investigated whether preconditioning with short-term DR attenuates chronic pressure overload-induced cardiac hypertrophy and associated oxidative stress.

Sphingolipids and Kidney Disease: Possible Role of Preeclampsia and Intrauterine Growth Restriction (IUGR).

Sphingolipids are now considered not only as constitutional components of the cellular membrane but also as essential bioactive factors regulating development and physiologic functions. Ceramide is a vital intermediate of sphingolipid metabolism, synthesized by and salvage pathways, producing multiple types of sphingolipids and their metabolites. Although mutations in gene-encoding enzymes regulating sphingolipid synthesis and metabolism cause distinct diseases, an abnormal sphingolipid metabolism contributes to various pathologic conditions, including kidney diseases.

Comparison of effects of L/N-type and L-type calcium channel blockers on post-infarct cardiac remodelling in spontaneously hypertensive rats.

Hypertension and coronary events are becoming more prevalent in aging societies, and myocardial infarction usually occurs in calcium channel blocker (CCB)-treated hypertensive patients. We herein compared the effects of cilnidipine, an L/N-type CCB and amlodipine, an L-type CCB, on post-infarct left ventricular (LV) remodelling in spontaneously hypertensive rats (SHRs). Male SHRs were subjected to 30 minutes of left coronary artery occlusion followed by reperfusion (MI group).

Antihypertensive and Renoprotective Effects of Dietary Flaxseed and its Mechanism of Action in Deoxycorticosterone Acetate-Salt Hypertensive Rats.

Background/aims: Flaxseed contains alpha-linolenic acid (ALA), lignans, and dietary fiber, and its intake lowers blood pressure in hypertensive patients. Here, we examined the effects of flaxseed powder, which includes all flaxseed components, flaxseed oil, composed mainly of ALA, flaxseed lignan, and flaxseed fiber, on hypertension and renal damage induced by deoxycorticosterone acetate (DOCA)-salt. Then, we investigated the mechanisms of action associated with the effects of flaxseed.

Transiently proliferating perivascular microglia harbor M1 type and precede cerebrovascular changes in a chronic hypertension model.

Background: Microglia play crucial roles in the maintenance of brain homeostasis. Activated microglia show a biphasic influence, promoting beneficial repair and causing harmful damage via M2 and M1 microglia, respectively. It is well-known that microglia are initially activated to the M2 state and subsequently switch to the M1 state, called M2-to-M1 class switching in acute ischemic models.

Extracellular matrix roles in cardiorenal fibrosis: Potential therapeutic targets for CVD and CKD in the elderly.

Whereas hypertension, diabetes, and dyslipidemia are age-related risk factors for cardiovascular disease (CVD) and chronic kidney disease (CKD), aging alone is an independent risk factor. With advancing age, the heart and kidney gradually but significantly undergo inflammation and subsequent fibrosis, which eventually results in an irreversible decline in organ physiology. Through cardiorenal network interactions, cardiac dysfunction leads to and responds to renal injury, and both facilitate aging effects.

Macrophage overexpression of matrix metalloproteinase-9 in aged mice improves diastolic physiology and cardiac wound healing after myocardial infarction.

Matrix metalloproteinase (MMP)-9 increases in the myocardium with advanced age and after myocardial infarction (MI). Because young transgenic (TG) mice overexpressing human MMP-9 only in macrophages show better outcomes post-MI, whereas aged TG mice show a worse aging phenotype, we wanted to evaluate the effect of aging superimposed on MI to see if the detrimental effect of aging counteracted the benefits of macrophage MMP-9 overexpression. We used 17- to 28-mo-old male and female C57BL/6J wild-type (WT) and TG mice ( n = 10-21 mice/group) to evaluate the effects of aging superimposed on MI.

Transgenic overexpression of macrophage matrix metalloproteinase-9 exacerbates age-related cardiac hypertrophy, vessel rarefaction, inflammation, and fibrosis.

Advancing age is an independent risk factor for cardiovascular disease. Matrix metalloproteinase-9 (MMP-9) is secreted by macrophages and robustly increases in the left ventricle (LV) with age. The present study investigated the effect of MMP-9 overexpression in macrophages on cardiac aging.

Pitavastatin suppresses hyperglycaemia-induced podocyte injury via bone morphogenetic protein-7 preservation.

Podocytes form the essential components of the glomerular filtration barrier and play a critical role in diabetic nephropathy. Recent evidence suggests that HMG-CoA reductase inhibitors (statins) exert renoprotective effects. We investigated whether pitavastatin directly suppresses hyperglycaemia-induced podocyte injury using cultured podocytes and, if so, the mechanism of the beneficial effects.

Increased ADAMTS1 mediates SPARC-dependent collagen deposition in the aging myocardium.

Secreted protein acidic and rich in cysteine (SPARC) is a collagen-binding matricellular protein highly expressed during fibrosis. Fibrosis is a prominent component of cardiac aging that reduces myocardial elasticity. Previously, we reported that SPARC deletion attenuated myocardial stiffness and collagen deposition in aged mice.

Pitavastatin Exhibits Protective Effects on Podocytes Accompanied by BMP-7 Up-Regulation and Rho Suppression.

Background/aims: Podocytes injury is involved in the development of diabetic nephropathy. This study was designed to confirm the reno- and podocyte-protective effects of pitavastatin in diabetic rats and clarify its mechanisms.

Methods: Wistar rats were divided into 4 treatment groups: control, streptozotocin (STZ; 55 mg/kg)-induced diabetes, STZ with pitavastatin (10 mg/kg/day), and STZ with tempol (1 mmol/l).

Short-Term Caloric Restriction Suppresses Cardiac Oxidative Stress and Hypertrophy Caused by Chronic Pressure Overload.

Background: Caloric restriction (CR) prevents senescent changes, in which reactive oxygen species (ROS) have a critical role. Left ventricular (LV) hypertrophy is a risk factor for cardiovascular diseases. We examined whether CR alters cardiac redox state and hypertrophy from chronic pressure overload.

Secreted protein acidic and rich in cysteine facilitates age-related cardiac inflammation and macrophage M1 polarization.

To investigate the role of secreted protein acidic and rich in cysteine (SPARC) in age-related cardiac inflammation, we studied six groups of mice: young (3-5 mo old), middle-aged (10-12 mo old), and old (18-29 mo old) C57BL/6 wild-type (WT) and SPARC-null (Null) mice (n = 7-10/group). Cardiac function and structure were determined by echocardiography. The left ventricle was used for cytokine gene array and macrophage quantification by immunohistochemistry.

Age and SPARC change the extracellular matrix composition of the left ventricle.

Secreted protein acidic and rich in cysteine (SPARC), a collagen-binding matricellular protein, has been implicated in procollagen processing and deposition. The aim of this study was to investigate age- and SPARC-dependent changes in protein composition of the cardiac extracellular matrix (ECM). We studied 6 groups of mice (n = 4/group): young (4-5 months old), middle-aged (11-12 m.

Cardiac aging is initiated by matrix metalloproteinase-9-mediated endothelial dysfunction.

Aging is linked to increased matrix metalloproteinase-9 (MMP-9) expression and extracellular matrix turnover, as well as a decline in function of the left ventricle (LV). Previously, we demonstrated that C57BL/6J wild-type (WT) mice > 18 mo of age show impaired diastolic function, which was attenuated by MMP-9 deletion. To evaluate mechanisms that initiate the development of cardiac dysfunction, we compared the LVs of 6-9- and 15-18-mo-old WT and MMP-9 null (Null) mice.

Myofibroblasts and the extracellular matrix network in post-myocardial infarction cardiac remodeling.

The cardiac extracellular matrix (ECM) fills the space between cells, supports tissue organization, and transduces mechanical, chemical, and biological signals to regulate homeostasis of the left ventricle (LV). Following myocardial infarction (MI), a multitude of ECM proteins are synthesized to replace myocyte loss and form a reparative scar. Activated fibroblasts (myofibroblasts) are the primary source of ECM proteins, thus playing a key role in cardiac repair.