Lipids in health and disease.

The discovery of regulated cell death presents tantalizing possibilities for gaining control over the life-death decisions made by cells in disease. Although apoptosis has been the focus of drug discovery for many years, recent research has identified regulatory mechanisms and signalling pathways for previously unrecognized, regulated necrotic cell death routines. Distinct critical nodes have been characterized for some of these alternative cell death routines, whereas other cell death routines are just beginning to be unravelled. In this Review, we describe forms of regulated necrotic cell death, including necroptosis, the emerging cell death modality of ferroptosis (and the related oxytosis) and the less well comprehended parthanatos and cyclophilin D-mediated necrosis. We focus on small molecules, proteins and pathways that can induce and inhibit these non-apoptotic forms of cell death, and discuss strategies for translating this understanding into new therapeutics for certain disease contexts.

Regulated necrosis: disease relevance and therapeutic opportunities

This monthly, peer-reviewed journal includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.

Molecular Medicine Reports

https://krishi.icar.gov.in/jspui/bitstream/123456789/28481/1/Nanotherapy_BIOPHA_2017.pdf

Nanotherapeutics: An insight into healthcare and multi-dimensional applications in medical sector of the modern world

We report a nanoparticulate system capable of targeting the heart after myocardial infarction (MI). Targeting is based on overexpression of angiotensin II type 1 (AT1) receptor in the infarcted heart. Liposomes 142 nm in diameter were conjugated with a ligand specific to AT1. The nanoparticles were able to specifically target cardiac cells in vitro, and in the infarcted heart after intravenous injection in vivo. This system may be useful for delivering therapeutic agents specifically to the infarcted heart.

Nanoparticles for targeting the infarcted heart

RGD modified and PEGylated lipid nanoparticles loaded with puerarin: Formulation, characterization and protective effects on acute myocardial ischemia model.

Background
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a recently identified and potentially useful plasma biomarker for cardiovascular and atherosclerotic diseases. However, the correlation between the Lp-PLA2 activity and carotid atherosclerosis remains poorly investigated in patients with metabolic syndrome (MetS). The present study aimed to evaluate the potential role of Lp-PLA2 as a comprehensive marker of metabolic syndrome in individuals with and without carotid atherosclerosis.

https://link.springer.com/content/pdf/10.1186/1476-511X-10-13.pdf

Plasma Lipoprotein-associated Phospholipase A2 in Patients with Metabolic Syndrome and Carotid Atherosclerosis

Myocardial infarction (MI) is defined as the deprivation of the myocardial tissue of oxygen and nutrients, resulting in the induction of inflammation and apoptosis of the cardiomyocytes. Poly (ADP‑ribose) polymerase 1 (PARP1) is a nuclear enzyme closely associated with MI, that can be activated by DNA damage. Inducible nitric oxide synthase (iNOS) is a critical enzyme among the inflammatory cytokines. The present study aimed to investigate the underlying mechanism of the protective effects of PARP1 and iNOS inhibitor against MI, in rats. A total of 40 male Wistar rats were divided into four groups. The rats were anesthetized with sodium pentobarbital (50 mg/kg), and the left anterior descending coronary artery was occluded by ligation, using a 6‑0 polypropylene monofilament suture, at the left atrial apex, in order to induce MI. The rats from each group received an abdominal injection of either dimethylsulfoxide (100 µl, for MI group); PARP‑1 inhibitor, 3,4‑dihydro‑5‑[4‑(1‑piperidinyl)butoxy]‑1(2H)‑ isoquinolinone (DPQ; 10 mg/kg); or iNOS inhibitor, N‑(1‑naphthyl)ethylenediamine dihydrochloride (1400W; 10 mg/kg). The hearts were harvested from the rats after four weeks. Inhibition of PARP and iNOS activity improved heart function, as determined by serial echocardiography. The rate of apoptosis, as determined by a terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling assay, was reduced by 39.71 and 39.00% in the DPQ and 1400W groups, respectively, and this was accompanied by the downregulated expression of cleaved caspase‑3 and PARP1. Effective inhibition of PARP and iNOS, by DPQ and 1400W, was detected by western blotting and immunofluorescence, and was shown to repress O2‑ and nitrotyrosine levels, following MI. The present study confirmed that inhibition of PARP1 and iNOS was able to protect against ischemic myocardial damage, by reducing the levels of apoptosis.

/pdf/inhibition-of-poly-adp-ribose-polymerase-and-inducible-1ztw8frriz.pdf

Inhibition of poly (ADP-ribose) polymerase and inducible nitric oxide synthase protects against ischemic myocardial damage by reduction of apoptosis

ObjectiveTo determine if high fasting blood glucose (FBG) level is an independent predictor of serious coronary lesions in patients with coronary artery disease (CAD).MethodsWe enrolled 64 patients...

https://journals.sagepub.com/doi/pdf/10.1177/0300060518798252

Predictive value of fasting blood glucose for serious coronary atherosclerosis in non-diabetic patients.

Objective. Hypoxia inducible factor-1α (HIF-1α) regulates many genes involved in angiogenesis during embryonic development. Epidermal growth factor-like domain 7 (Egfl7) is a specific marker for human arterial endothelial cells that are in an activated state of proliferation, migration, and remodeling. This study evaluates the intricate relationship between HIF-1α and Egfl7 under both hyperoxia and hypoxia states. Methods. The neonatal mice were exposed to either hyperoxia or hypoxia in order to detect the pulmonary and cardiac Egfl7 messenger RNA (mRNA) or protein expression regulated by oxygen tension in vivo by reverse transcriptase polymerase chain reaction or immunohistochemistry staining. Egfl7 expression in HIF-1α null pulmonary endothelial cells in hypoxia conditions and effects of overexpression or knockdown of HIF-1α on Egfl7 expression in human umbilical vein endothelial cells would be clarified in vitro by reverse transcriptase polymerase chain reaction and Western blot, respectively. ...

Qing-Hua Lu

Papers

RGD modified and PEGylated lipid nanoparticles loaded with puerarin: Formulation, characterization and protective effects on acute myocardial ischemia model.

Plasma Lipoprotein-associated Phospholipase A2 in Patients with Metabolic Syndrome and Carotid Atherosclerosis

Inhibition of poly (ADP-ribose) polymerase and inducible nitric oxide synthase protects against ischemic myocardial damage by reduction of apoptosis

Predictive value of fasting blood glucose for serious coronary atherosclerosis in non-diabetic patients.

The expression of epidermal growth factor-like domain 7 regulated by oxygen tension via hypoxia inducible factor (HIF)-1α activity.