Sepsis and high-density lipoproteins: Pathophysiology and potential new therapeutic targets.

In 2020, sepsis has been defined a worldwide health major issue (World Health Organization). Lung, urinary tract and abdominal cavity are the preferred sites of sepsis-linked infection. Research has highlighted that the advancement of sepsis is not only related to the presence of inflammation or microbial or host pattern recognition.

Pathophysiology of bone remodelling cycle: Role of immune system and lipids.

Osteoporosis is the most common skeletal disease worldwide, characterized by low bone mineral density, resulting in weaker bones, and an increased risk of fragility fractures. The maintenance of bone mass relies on the precise balance between bone synthesis and resorption. The close relationship between the immune and skeletal systems, called "osteoimmunology", was coined to identify these overlapping "scientific worlds", and its function resides in the evaluation of the mutual effects of the skeletal and immune systems at the molecular and cellular levels, in both physiological and pathological states.

Effects of Marine-Derived Components on Cardiovascular Disease Risk Factors and Gut Microbiota Diversity.

Cardiovascular diseases (CVDs), which comprise coronary heart disease, hypertension, and stroke, collectively represent the number one cause of death globally. Atherosclerosis is the dominant cause of CVDs, and its risk factors are elevated levels of low-density lipoprotein cholesterol and triglycerides, hypertension, cigarette smoking, obesity, and diabetes mellitus. In addition, diverse evidence highlights the role played by inflammation and clonal haematopoiesis, eventually leading to immunity involvement.

The Role of Marine n-3 Polyunsaturated Fatty Acids in Inflammatory-Based Disease: The Case of Rheumatoid Arthritis.

Inflammation is a conserved process that involves the activation of immune and non-immune cells aimed at protecting the host from bacteria, viruses, toxins and injury. However, unresolved inflammation and the permanent release of pro-inflammatory mediators are responsible for the promotion of a condition called "low-grade systemic chronic inflammation", which is characterized by tissue and organ damage, metabolic changes and an increased susceptibility to non-communicable diseases. Several studies have demonstrated that different dietary components may influence modifiable risk factors for diverse chronic human pathologies.

Marine n-3 polyunsaturated fatty acids: Efficacy on inflammatory-based disorders.

Inflammation is a physiological response to injury, stimulating tissue repair and regeneration. However, the presence of peculiar individual conditions can negatively perturb the resolution phase eventually leading to a state of low-grade systemic chronic inflammation, characterized by tissue and organ damages and increased susceptibility to non-communicable disease. Marine n-3 polyunsaturated fatty acids (n-3 PUFAs), mainly eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), are able to influence many aspects of this process.

Biotechnology Approaches for the Treatment of Dyslipidemia.

Background: Despite advances in the development of lipid-lowering therapies, clinical trials have shown that a significant residual risk of cardiovascular disease persists. Specifically, new drugs are needed for non-responding or statin-intolerant subjects or patients considered at very high risk for cardiovascular events even though are already on treatment with the best standard of care.

Results And Conclusions: Besides, genetic and epidemiological studies and Mendelian randomization analyses have strengthened the linear correlation between the concentration of low-density lipoprotein cholesterol (LDL-C) and the incidence of cardiovascular events and highlighted various novel therapeutic targets.

The mutual interplay of gut microbiota, diet and human disease.

The intestinal milieu harbours the gut microbiota, consisting of a complex community of bacteria, archaea, fungi, viruses and protozoans that bring to the host organism an endowment of cells and genes more numerous than its own. In the last 10 years, mounting evidence has highlighted the prominent influence of the gut mutualistic bacterial communities on human health. Microbial colonization occurs alongside with immune system development and plays a role in intestinal physiology.

A Compendium of the Biological Effects of Apolipoprotein A-I.

Obesity is a pathologic condition generated by an energy imbalance, that is, excess caloric consumption, leading to weight gain and metabolic disturbances characterized by adipose tissue inflammation and hyperglycemic conditions. In line with these observations, increasing evidence causally links inflammation, or the molecules and networks integral to inflammatory response, to the development of obesity and the complications that emerge from this pathology, such as cardiovascular, neurologic, respiratory, and metabolic illnesses, as well as sepsis and cancer. Not surprisingly, this chronic and abnormal metabolic background leads to constant derangements in innate and adaptive immunity.

Infusions of Large Synthetic HDL Containing Trimeric apoA-I Stabilize Atherosclerotic Plaques in Hypercholesterolemic Rabbits.

Background: Among strategies to reduce the remaining risk of cardiovascular disease, interest has focused on using infusions of synthetic high-density lipoprotein (sHDL).

Methods: New Zealand rabbits underwent a perivascular injury at both carotids and were randomly allocated into 2 protocols: (1) a single-dose study, where rabbits were treated with a single infusion of sHDL containing a trimeric form of human apoA-I (TN-sHDL, 200 mg/kg) or with Placebo; (2) a multiple-dose study, where 4 groups of rabbits were treated 5 times with Placebo or TN-sHDL at different doses (8, 40, 100 mg/kg). Plaque changes were analysed in vivo by intravascular ultrasound.

Effects of Fish n-3 PUFAs on Intestinal Microbiota and Immune System.

Studies over several decades have documented the beneficial actions of n-3 polyunsaturated fatty acids (PUFAs), which are plentiful in fish oil, in different disease states. Mechanisms responsible for the efficacy of n-3 PUFAs include: (1) Reduction of triglyceride levels; (2) anti-arrhythmic and antithrombotic effects, and (3) resolution of inflammatory processes. The human microbiota project and subsequent studies using next-generation sequencing technology have highlighted that thousands of different microbial species are present in the human gut, and that there has been a significant variability of taxa in the microbiota composition among people.

Effects of Vegetable Proteins on Hypercholesterolemia and Gut Microbiota Modulation.

Risk assessment tools, i.e., validated risk prediction algorithms, to estimate the patient's 10-year risk of developing cardiovascular disease (CVD) should be used to identify high-risk people for primary prevention.

Lipid phosphate phosphatase 3 in vascular pathophysiology.

LPP3 is an integral membrane protein belonging to a family of enzymes (LPPs) that display broad substrate specificity and catalyse dephosphorylation of several lipid substrates, including lysophosphatidic acid and sphingosine-1-phosphate. In mammals, the LPP family consists of three enzymes named LPP1, LPP2 and LPP3, which are encoded by three independent genes, PLPP1, PLPP2 and PLPP3, respectively (formerly known as PPAP2A, PPAP2C, PPAP2B). These three enzymes, in vitro, do not seem to differ for catalytic activities and substrate preferences.

Effect of Dietary Components from Antarctic Krill on Atherosclerosis in apoE-Deficient Mice.

Scope: Antarctic krill is a great source of n-3 fatty acids and high-quality proteins. Aim of the study was to evaluate the effect of Antarctic krill components on plasma lipids and atherosclerosis development.

Methods And Results: Sixty apoEKO mice were divided into four groups and fed Western diet (CONTROL) or Western-like diets, differing for protein or fat content.

Liver-specific deletion of the Plpp3 gene alters plasma lipid composition and worsens atherosclerosis in apoE mice.

The PLPP3 gene encodes for a ubiquitous enzyme that dephosphorylates several lipid substrates. Genome-wide association studies identified PLPP3 as a gene that plays a role in coronary artery disease susceptibility. The aim of the study was to investigate the effect of Plpp3 deletion on atherosclerosis development in mice.

Nutraceuticals and Bioactive Components from Fish for Dyslipidemia and Cardiovascular Risk Reduction.

Cardiovascular disease remains the most common health problem in developed countries, and residual risk after implementing all current therapies is still high. Permanent changes in lifestyle may be hard to achieve and people may not always be motivated enough to make the recommended modifications. Emerging research has explored the application of natural food-based strategies in disease management.

High-density lipoprotein deficiency in genetically modified mice deeply affects skin morphology: A structural and ultrastructural study.

Cutaneous lipids, endogenously synthetized and transported by lipoproteins, play a pivotal role in maintaining skin barrier. An impairment of extracutaneous lipid trafficking leads to the development of xanthomas, mostly arising in hyperlipidemic patients, but also in subjects with high-density lipoprotein (HDL) deficiency. The aim of this work was to evaluate, in a genetically modified mouse model, lacking two protein components of HDL particles, apolipoprotein(apo)E and apoA-I, the effect of HDL deficiency on skin morphology.

A salmon protein hydrolysate exerts lipid-independent anti-atherosclerotic activity in ApoE-deficient mice.

Fish consumption is considered health beneficial as it decreases cardiovascular disease (CVD)-risk through effects on plasma lipids and inflammation. We investigated a salmon protein hydrolysate (SPH) that is hypothesized to influence lipid metabolism and to have anti-atherosclerotic and anti-inflammatory properties. 24 female apolipoprotein (apo) E(-/-) mice were divided into two groups and fed a high-fat diet with or without 5% (w/w) SPH for 12 weeks.

Magnetic resonance imaging visualization of vulnerable atherosclerotic plaques at the brachiocephalic artery of apolipoprotein E knockout mice by the blood-pool contrast agent B22956/1.

The aim of this study was to identify, by magnetic resonance imaging (MRI), the ability of the blood-pool contrast agent B22956/1 to detect atherosclerotic plaques developing at the brachiocephalic artery of apolipoprotein E knockout (apoE-KO) mice and to possibly identify vulnerable atherosclerotic lesions. After high-fat feeding for 8 or 12 weeks, MRIs of brachiocephalic arteries were acquired before and after B22956/1 administration; then vessels were removed and analyzed by histology. B22956/1 injection caused a rapid increase in plaque signal enhancement and plaque to muscle contrast values, which remained stable up to 70 minutes.

An immunomodulating fatty acid analogue targeting mitochondria exerts anti-atherosclerotic effect beyond plasma cholesterol-lowering activity in apoe(-/-) mice.

Tetradecylthioacetic acid (TTA) is a hypolipidemic antioxidant with immunomodulating properties involving activation of peroxisome proliferator-activated receptors (PPARs) and proliferation of mitochondria. This study aimed to penetrate the effect of TTA on the development of atherosclerotic lesions in apolipoprotein (apo)-E(-/-) mice fed a high-fat diet containing 0.3% TTA for 12 weeks.