fatty acids affect cardiac function (including antiarrhythmic effects), hemodynamics (cardiac mechanics), and arterial endothelial function have helped clarify potential mechanisms of action. The present Statement will address distinctions between plant-derived (-linolenic acid, C18:3n-3) and marine-derived (eicosapentaenoic acid, C20:5n-3 [EPA] and docosahexaenoic acid, C22:6n-3 [DHA]) omega-3 fatty acids. (Unless otherwise noted, the term omega-3 fatty acids will refer to the latter.) Evidence from epidemiological studies and RCTs will be reviewed, and recommendations reflecting the current state of knowledge will be made with regard to both fish consumption and omega-3 fatty acid (plant- and marine-derived) supplementation. This will be done in the context of recent guidance issued by the US Environmental Protection Agency and the Food and Drug Administration (FDA) about the presence of environmental contaminants in certain species of fish.

http://www.hearthealthynaturalbeef.com/americanheartassociationnov192002.pdf

Fish Consumption, Fish Oil, Omega-3 Fatty Acids, and Cardiovascular Disease

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.

https://biblio.ugent.be/publication/8555786/file/8555788.pdf

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Byproducts of normal mitochondrial metabolism and homeostasis include the buildup of potentially damaging levels of reactive oxygen species (ROS), Ca2+, etc., which must be normalized. Evidence suggests that brief mitochondrial permeability transition pore (mPTP) openings play an important physiological role maintaining healthy mitochondria homeostasis. Adaptive and maladaptive responses to redox stress may involve mitochondrial channels such as mPTP and inner membrane anion channel (IMAC). Their activation causes intra- and intermitochondrial redox-environment changes leading to ROS release. This regenerative cycle of mitochondrial ROS formation and release was named ROS-induced ROS release (RIRR). Brief, reversible mPTP opening-associated ROS release apparently constitutes an adaptive housekeeping function by the timely release from mitochondria of accumulated potentially toxic levels of ROS (and Ca2+). At higher ROS levels, longer mPTP openings may release a ROS burst leading to destruction of mitochondria, and if propagated from mitochondrion to mitochondrion, of the cell itself. The destructive function of RIRR may serve a physiological role by removal of unwanted cells or damaged mitochondria, or cause the pathological elimination of vital and essential mitochondria and cells. The adaptive release of sufficient ROS into the vicinity of mitochondria may also activate local pools of redox-sensitive enzymes involved in protective signaling pathways that limit ischemic damage to mitochondria and cells in that area. Maladaptive mPTP- or IMAC-related RIRR may also be playing a role in aging. Because the mechanism of mitochondrial RIRR highlights the central role of mitochondria-formed ROS, we discuss all of the known ROS-producing sites (shown in vitro) and their relevance to the mitochondrial ROS production in vivo.

Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release

In 2009, the Nomenclature Committee on Cell Death (NCCD) proposed a set of recommendations for the definition of distinct cell death morphologies and for the appropriate use of cell death-related terminology, including 'apoptosis', 'necrosis' and 'mitotic catastrophe'. In view of the substantial progress in the biochemical and genetic exploration of cell death, time has come to switch from morphological to molecular definitions of cell death modalities. Here we propose a functional classification of cell death subroutines that applies to both in vitro and in vivo settings and includes extrinsic apoptosis, caspase-dependent or -independent intrinsic apoptosis, regulated necrosis, autophagic cell death and mitotic catastrophe. Moreover, we discuss the utility of expressions indicating additional cell death modalities. On the basis of the new, revised NCCD classification, cell death subroutines are defined by a series of precise, measurable biochemical features.

/pdf/molecular-definitions-of-cell-death-subroutines-q5g428rlyi.pdf

Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012

The first suggestion that physical exercise results in free radical-mediated damage to tissues appeared in 1978, and the past three decades have resulted in a large growth of knowledge regarding exercise and oxidative stress. Although the sources of oxidant production during exercise continue to be debated, it is now well established that both resting and contracting skeletal muscles produce reactive oxygen species and reactive nitrogen species. Importantly, intense and prolonged exercise can result in oxidative damage to both proteins and lipids in the contracting myocytes. Furthermore, oxidants can modulate a number of cell signaling pathways and regulate the expression of multiple genes in eukaryotic cells. This oxidant-mediated change in gene expression involves changes at transcriptional, mRNA stability, and signal transduction levels. Furthermore, numerous products associated with oxidant-modulated genes have been identified and include antioxidant enzymes, stress proteins, DNA repair proteins, and mitochondrial electron transport proteins. Interestingly, low and physiological levels of reactive oxygen species are required for normal force production in skeletal muscle, but high levels of reactive oxygen species promote contractile dysfunction resulting in muscle weakness and fatigue. Ongoing research continues to probe the mechanisms by which oxidants influence skeletal muscle contractile properties and to explore interventions capable of protecting muscle from oxidant-mediated dysfunction.

/pdf/exercise-induced-oxidative-stress-cellular-mechanisms-and-4a18810890.pdf

Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production

A part of his ‘theory of haematopoiesis’, Alexander Maksimov first proposed the existence of stem cells circa 1908. The importance and role of stem cells remained shrouded until the early 1960s when Becker and colleagues demonstrated self-renewing haematopoietic cells in mouse spleen [1], and Joseph Altman first examined neurogenesis in the mammalian adult brain [2]. In the 1980s, two groups simultaneously reported the ability to i i h t t t a w a a v d r o c d t l i i t s t m m c a u

Developing stem cell therapeutics for the heart also requires targeting non-myocytes.

The other second messenger gas: carbon monoxide signalling for myocardial protection?

Adipose tissue is now acknowledged as not just an energy storage tissue, but also as an endocrine organ that produces bioactive adipokines. Omentin is an adipokine that is gaining interest due to reports of reduced circulating plasma levels in obesity and blood vessel diseases. An emerging cardioprotective role for omentin is discussed.

Omentin on a Four-Pronged Fork: Another Reason Why Obesity Erodes Cardiovascular Survival

A key feature of advanced age is a reduced threshold for excess Ca2+ loading during events that stimulate increased Ca2+ entry, such as augmented cardiac work, oxidative stress or post-ischemic reflow. Remodeling of myocardial cell membranes is a major factor underlying the relative Ca2+ intolerance in senescence and greater vulnerability to ischemic injury. In addition to cell death, surviving myocytes increase in size and exhibit altered gene expression of key effector proteins, including those that sustain Ca2+ homeostasis. Age-associated membrane changes, that may also be influenced by diet, include increases in membrane rigidity, cholesterol, phosphatidylcholine, omega-6 polyunsaturated fatty acids (PUFA), 4-hydroxy-2-nonenal, and decreases in omega-3 PUFA, cardiolipin. These alterations have profound consequences on the efficacy of membrane proteins involved with ion homeostasis, signal transduction, redox reactions and oxidative phosphorylation. However, some of the age-related detrimental adaptations may be beneficially modified by dietary strategy. Diet rich in omega-3 PUFA reverses the age-associated membrane omega-3: omega-6 PUFA imbalance, and dysfunctional Ca2+ metabolism, facilitating increased efficiency of mitochondrial energy production and improved tolerance of ischemia and reperfusion.

Salvatore Pepe

Papers

Developing stem cell therapeutics for the heart also requires targeting non-myocytes.

The other second messenger gas: carbon monoxide signalling for myocardial protection?

Omentin on a Four-Pronged Fork: Another Reason Why Obesity Erodes Cardiovascular Survival

Aging and Dietary Lipids Modulate Ca2+-Dependent Mitochondrial Function in the Post-Ischemic Heart

The challenge of cardiovascular gene therapy in humans