Rhythmic Contractions of Lymph Vessels and Lymph Flow Are Disrupted in Hypertensive Rats.

Background: Hypertension increases the risk of lymphedema in patients with comorbidities, but whether hypertension directly compromises lymph vessel (LV) function and lymph flow is unclear. We compared the contractions of mesenteric LVs ex vivo and lymph flow in vivo between normotensive and Ang II (angiotensin II)-induced hypertensive rats and explored the ionic basis of contractile patterns. Key studies were recapitulated in spontaneously hypertensive rats and control Wistar-Kyoto rats.

Real-Time Evaluation of Absolute, Cytosolic, Free Ca2+ and Corresponding Contractility in Isolated, Pressurized Lymph Vessels.

The lymphatic vasculature, now often referred to as "the third circulation," is located in many vital organ systems. A principal mechanical function of the lymphatic vasculature is to return fluid from extracellular spaces back to the central venous ducts. Lymph transport is mediated by spontaneous rhythmic contractions of lymph vessels (LVs).

Doxorubicin‑induced cardiomyopathy is mitigated by empagliflozin via the modulation of endoplasmic reticulum stress pathways.

Doxorubicin (Dox) exhibits a high efficacy in the treatment of numerous types of cancer. However, the beneficial cytotoxic effects of Dox are often accompanied by an increase in the risk of cardiotoxicity. Oxidative stress (OS) plays a key role in Dox‑induced cardiomyopathy (DIC).

Lipidomic Predictors of Coronary No-Reflow.

The ‘no-reflow’ phenomenon (NRP) after primary percutaneous coronary intervention (PCI) is a serious complication among acute ST-segment elevation myocardial infarction (STEMI) patients. Herein, a comprehensive lipidomics approach was used to quantify over 300 distinct molecular species in circulating plasma from 126 patients with STEMI before and after primary PCI. Our analysis showed that three lipid classes: phosphatidylcholine (PC), alkylphosphatidylcholine (PC(O)), and sphingomyelin (SM), were significantly elevated (p < 0.

Olive oil protects against progression of heart failure by inhibiting remodeling of heart subsequent to myocardial infarction in rats.

We examined the beneficial effects of olive oil against heart failure post-myocardial infarction (PMI), induced by coronary artery ligation in rats. Animals were divided into sham and ligated groups and fed either regular chow, olive oil (10% wt/wt), or corn oil (10% wt/wt) and were followed up to 16 weeks. On the echocardiography at 3 days (PMI), in the ligated regular chow (LRC), ligated olive oil (LOO), and ligated corn oil (LCO) left ventricular ejection fraction (LVEF) decrease was 12.

NF-κB, A Potential Therapeutic Target in Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are the leading cause of death globally. Atherosclerosis is the basis of major CVDs - myocardial ischemia, heart failure, and stroke. Among numerous functional molecules, the transcription factor nuclear factor κB (NF-κB) has been linked to downstream target genes involved in atherosclerosis.

The structural basis of effective LOX-1 inhibition.

Along with other scavenger receptors, splice variants of LOX-1 play an important role in modulating numerous subcellular mechanisms such as normal cell development, differentiation and growth in response to physiological stimuli. Thus, LOX-1 activity is a key regulator in determining the severity of many genetic, metabolic, cardiovascular, renal, and neurodegenerative diseases and/or cancer. Increased expression of LOX-1 precipitates pathological disorders during the aging process.

Interleukin-10 Mitigates Doxorubicin-Induced Endoplasmic Reticulum Stress as Well as Cardiomyopathy.

The use of doxorubicin (Dox) in cancer patients carries the risk of cardiotoxicity via an increase in oxidative stress, mitochondrial dysfunction, and disturbed endoplasmic reticulum (ER) homeostasis in cardiomyocytes. The present study explores which of the ER transmembrane sensors is involved in Dox-induced apoptosis and whether interleukin-10 (IL-10) has any mitigating effect. There was a time-related increase in apoptosis in cardiomyocytes exposed to 5.

Endoplasmic Reticulum Stress Promotes iNOS/NO and Influences Inflammation in the Development of Doxorubicin-Induced Cardiomyopathy.

Doxorubicin (Dox) is known to cause heart failure in some cancer patients. Despite extensive studies over the past half century, the subcellular basis of Dox-induced cardiomyopathy (DIC) is still elusive. Earlier, we suggested that Dox causes a delayed activation of unfolded protein response (UPR) which may promote mitochondrial Bax activity leading to cardiomyocyte death.

Role of oxidative stress versus lipids in monocrotaline-induced pulmonary hypertension and right heart failure.

Pulmonary hypertension (PH) is a global health issue with a prevalence of 10% in ages >65 years. Right heart failure (RHF) is the main cause of death in PH. We have previously shown that monocrotaline (MCT)-induced PH and RHF are due to an increase in oxidative stress.

Study of ER stress and apoptotic proteins in the heart and tumor exposed to doxorubicin.

Although a high cumulative dose of Doxorubicin (Dox) is known to cause cardiotoxicity, there is still a lack of understanding of the subcellular basis of this drug-induced cardiomyopathy. Differential effects of Dox on mitochondria and endoplasmic reticulum (ER) were examined in cardiomyocytes, tumor cells, implanted tumors and hearts of normal as well as tumor-bearing animals. Dox increased mitochondrial (Mito) Bax activation at 3 h in the cardiomyocyte without change in the DNA damage inducible transcriptor-3 (DDIT3) expression in the ER.

Vitamin C: historical perspectives and heart failure.

Vitamin C (Vit C) is an ideal antioxidant as it is easily available, water soluble, very potent, least toxic, regenerates other antioxidants particularly Vit E, and acts as a cofactor for different enzymes. It has received much attention due to its ability in limiting reactive oxygen species, oxidative stress, and nitrosative stress, as well as it helps to maintain some of the normal metabolic functions of the cell. However, over 140 clinical trials using Vit C in different pathological conditions such as myocardial infarction, gastritis, diabetes, hypertension, stroke, and cancer have yielded inconsistent results.

IL-10 attenuates OxPCs-mediated lipid metabolic responses in ischemia reperfusion injury.

Oxidized phospholipids (OxPLs) promote inflammation as well as low density lipoprotein (LDL) uptake in a variety of physiological and pathological states. Given the anti-inflammatory role of the cytokine IL-10, we investigated its modulatory effect on the production of oxidized phosphatidylcholines (OxPCs) as well as lipid metabolic responses in global myocardial ischemia/reperfusion (I/R) injury. Increased OxPCs levels, by 1-Palmitoyl-2-(5-oxovaleryl)-sn-glycero-3-phosphocholine (POVPC), promoted oxidative stress (OS) and cell death.

Blueberry extract attenuates doxorubicin-induced damage in H9c2 cardiac cells .

The objective of this study was to analyze the cardioprotective roles of 3 wild blueberry genotypes and one commercial blueberry genotype by measuring markers of oxidative stress and cell death in H9c2 cardiac cells exposed to doxorubicin. Ripe berries of the 3 wild blueberry genotypes were collected from a 10-year-old clearcut forest near Nipigon, Ontario, Canada (49°1'39″N, 87°52'21″W), whereas the commercial blueberries were purchased from a local grocery store. H9c2 cardiac cells were incubated with 15 μg gallic acid equivalent/mL blueberry extract for 4 h followed by 5 μM doxorubicin for 4 h, and oxidative stress and active caspase 3/7 were analyzed.

Molecular hydrogen: potential in mitigating oxidative-stress-induced radiation injury .

Uncontrolled production of oxygen and nitrogen radicals results in oxidative and nitrosative stresses that impair cellular functions and have been regarded as causative common denominators of many pathological processes. In this review, we report on the beneficial effects of molecular hydrogen in scavenging radicals in an artificial system of OH formation. As a proof of principle, we also demonstrate that in rat hearts in vivo, administration of molecular hydrogen led to a significant increase in superoxide dismutase as well as pAKT, a cell survival signaling molecule.

Innate immune response in the pathogenesis of heart failure in survivors of myocardial infarction.

Among the different cardiovascular disease complications, atherosclerosis-induced myocardial infarction (MI) is the major contributor of heart failure (HF) and loss of life. This review presents short- and long-term features of post-MI in human hearts and animal models. It is known that the heart does not regenerate, and thus loss of cardiac cells after an MI event is permanent.

Vitamin C mitigates oxidative/nitrosative stress and inflammation in doxorubicin-induced cardiomyopathy.

Increase in oxidative/nitrosative stress is one of the mechanisms associated with the development of cardiotoxicity due to doxorubicin (Dox), a potent chemotherapy drug. Previously, we reported mitigation of Dox-induced oxidative/nitrosative stress and apoptosis by vitamin C (Vit C) in isolated cardiomyocytes. In the present in vivo study in rats, we investigated the effect of prophylactic treatment with Vit C on Dox-induced apoptosis, inflammation, oxidative/nitrosative stress, cardiac dysfunction, and Vit C transporter proteins.

Toll-like receptor 2 dominance over Toll-like receptor 4 in stressful conditions for its detrimental role in the heart.

It has been suggested that Toll-like receptor (TLR)4 promotes IL-10-mediated cardiac cell survival, whereas another receptor, TLR2, from the same family, is detrimental. Here, we examined the interactive role of these two innate signaling molecules under stressful conditions, including IL-10 knockout (IL-10) mice, global ischemia-reperfusion (I/R) injury in rat hearts, and in vitro short hairpin RNA experimental models in the presence or absence of IL-10 (10 ng/ml). Circulating and myocardial levels of TNF-α as well as apoptosis and fibrosis were higher in IL-10 mice.

Doxorubicin-induced nitrosative stress is mitigated by vitamin C via the modulation of nitric oxide synthases.

An increase in oxidative stress is suggested to be the main cause in Doxorubicin (Dox)-induced cardiotoxicity. However, there is now evidence that activation of inducible nitric oxide synthase (iNOS) and nitrosative stress are also involved. The role of vitamin C (Vit C) in the regulation of nitric oxide synthase (NOS) and reduction of nitrosative stress in Dox-induced cardiotoxicity is unknown.

Insulin resistance: an additional risk factor in the pathogenesis of cardiovascular disease in type 2 diabetes.

Sedentary life style and high calorie dietary habits are prominent leading cause of metabolic syndrome in modern world. Obesity plays a central role in occurrence of various diseases like hyperinsulinemia, hyperglycemia and hyperlipidemia, which lead to insulin resistance and metabolic derangements like cardiovascular diseases (CVDs) mediated by oxidative stress. The mortality rate due to CVDs is on the rise in developing countries.

Interleukin-10 activates Toll-like receptor 4 and requires MyD88 for cardiomyocyte survival.

Toll-like receptors (TLRs) are important in a variety of inflammatory diseases including acute cardiac disorders. TLR4 innate signaling regulates the synthesis of anti-inflammatory cytokine, interleukin-10 (IL-10) upon TLR4 agonists' re-stimulation. Anti-apoptotic action of IL-10 in cardiac dysfunction is generally accepted but its protective mechanism through TLR4 is not yet understood.

Oleic acid mitigates TNF-α-induced oxidative stress in rat cardiomyocytes.

Some of the effects of tumor necrosis factor alpha (TNF-α) are suggested to be mediated by oxidative stress. It has also been reported that dietary supplements of olive oil result in a reduction in LDL, oxidative stress, and blood pressure and these effects are attributed to oleic acid (OA)-a major component of olive oil. The objective of this study was to examine the beneficial effects of OA against TNF-α-induced oxidative stress and cardiomyocytes injury.

Akt regulates IL-10 mediated suppression of TNFα-induced cardiomyocyte apoptosis by upregulating Stat3 phosphorylation.

Background: We have already reported that TNF-α increases cardiomyocyte apoptosis and IL-10 treatment prevented these effects of TNF-α. Present study investigates the role of Akt and Jak/Stat pathway in the IL-10 modulation of TNF-α induced cardiomyocyte apoptosis.

Methodology/principal Findings: Cardiomyocytes isolated from adult Sprague Dawley rats were exposed to TNF-α (10 ng/ml), IL-10 (10 ng/ml) and TNF-α+IL-10 (ratio 1) for 4 h.

Subcellular basis of vitamin C protection against doxorubicin-induced changes in rat cardiomyocytes.

Understanding the molecular basis of doxorubicin (Dox)-induced cardiomyopathy is crucial to finding cardioprotective strategies. Oxidative stress-mediated pathways are known to contribute to cardiomyocyte apoptosis due to Dox. Improving the antioxidant defenses of cardiomyocytes could be one strategy for cardiac protection.