Nicotinamide riboside: A promising therapy for MI-induced acute kidney injury by upregulating nicotinamide phosphoribosyltransferase-mediated NAD levels.

Background: Cardiorenal syndrome (CRS) type 1 is characterized by the development of acute kidney injury (AKI) following acute cardiac illness and notably acute myocardial infarction (MI). AKI is considered an independent risk factor increasing mortality rate substantially. Nicotinamide dinucleotide (NAD) is an important coenzyme in energy metabolism and oxidative phosphorylation and in its oxidized form, a substrate for multiple NAD -dependent enzymes such as Sirtuins and poly-ADP ribose polymerases.

Potential Alternative Receptors for SARS-CoV-2-Induced Kidney Damage: TLR-4, KIM-1/TIM-1, and CD147.

Kidney damage in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can occur even in patients with no underlying kidney disease. Signs of kidney problems can progress to a state that demands dialysis and hampering recovery. Although not without controversy, emerging evidence implicates direct infectivity of SARS-CoV-2 in the kidney.

Nicotinamide Riboside Supplementation Restores Myocardial Nicotinamide Adenine Dinucleotide Levels, Improves Survival, and Promotes Protective Environment Post Myocardial Infarction.

Aims: Myocardial infarction (MI) is a major cause of death. Nicotinamide adenine dinucleotide (NAD) is a coenzyme in oxidative phosphorylation and substrate of sirtuins and poly-ADP ribose polymerases, enzymes critical for cardiac remodeling post-MI. Decreased NAD is reported in several heart failure models with paradoxically an upregulation of nicotinamide riboside kinase 2, which uses nicotinamide riboside (NR) as substrate in an NAD biosynthetic pathway.

Modulation of cardiac cAMP signaling by AMPK and its adjustments in pressure overload-induced myocardial dysfunction in rat and mouse.

The beta-adrenergic system is a potent stimulus for enhancing cardiac output that may become deleterious when energy metabolism is compromised as in heart failure. We thus examined whether the AMP-activated protein kinase (AMPK) that is activated in response to energy depletion may control the beta-adrenergic pathway. We studied the cardiac response to beta-adrenergic stimulation of AMPKα2-/- mice or to pharmacological AMPK activation on contractile function, calcium current, cAMP content and expression of adenylyl cyclase 5 (AC5), a rate limiting step of the beta-adrenergic pathway.

Assessing the outcomes of prescribing angiotensin converting enzyme inhibitors and angiotensin receptor blockers for COVID-19 patients.

Background: Patients with heart failure were affected severely by COVID-19. Most heart failure patients are on guideline directed medical therapy, which includes ACE inhibitors (ACEI) and ARBs. These medications were controversial at the beginning of the pandemic due to their interplay with the receptor that SARS-CoV-2 binds in the lungs.

Risk of thromboembolic events in non-hospitalized COVID-19 patients: A systematic review.

The risk of thromboembolism in non-hospitalized COVID-19 patients remains uncertain and was assessed in this review to better weigh benefits vs. risks of prophylactic anticoagulation in this population. A search was performed through three databases: Medline, Embase, and Cochrane Library until 2022.

Sexual dimorphism in acute myocardial infarction-induced acute kidney injury: cardiorenal deteriorating effects of ovariectomy in premenopausal female mice.

Acute kidney injury (AKI) is a common complication of cardiovascular diseases (CVDs) in both males and females, increasing mortality rate substantially. Premenopausal females appear to be more protected, suggesting a potential protective role of female sex hormones. Here, we tested the hypothesis that ovariectomy (OVX) eliminates the beneficial effect of female sex on renal protection following acute myocardial infarction (MI).

Interrelation between α-Cardiac Actin Treadmilling and Myocardin-Related Transcription Factor-A Nuclear Shuttling in Cardiomyocytes.

Myocardin-related transcription factors (MRTFs) play a central role in the regulation of actin expression and cytoskeletal dynamics that are controlled by Rho GTPases. SRF is a ubiquitous transcription factor strongly expressed in muscular tissues. The depletion of SRF in the adult mouse heart leads to severe dilated cardiomyopathy associated with the down-regulation of target genes encoding sarcomeric proteins including α-cardiac actin.

Ferulic Acid, Pterostilbene, and Tyrosol Protect the Heart from ER-Stress-Induced Injury by Activating SIRT1-Dependent Deacetylation of eIF2α.

Disturbances in Endoplasmic Reticulum (ER) homeostasis induce ER stress, which has been involved in the development and progression of various heart diseases, including arrhythmias, cardiac hypertrophy, ischemic heart diseases, dilated cardiomyopathy, and heart failure. A mild-to-moderate ER stress is considered beneficial and adaptative for heart functioning by engaging the pro-survival unfolded protein response (UPR) to restore normal ER function. By contrast, a severe or prolonged ER stress is detrimental by promoting cardiomyocyte apoptosis through hyperactivation of the UPR pathways.

Nitrate consumption preserves HFD-induced skeletal muscle mitochondrial ADP sensitivity and lysine acetylation: A potential role for SIRT1.

Dietary nitrate supplementation, and the subsequent serial reduction to nitric oxide, has been shown to improve glucose homeostasis in several pre-clinical models of obesity and insulin resistance. While the mechanisms remain poorly defined, the beneficial effects of nitrate appear to be partially dependent on AMPK-mediated signaling events, a central regulator of metabolism and mitochondrial bioenergetics. Since AMPK can activate SIRT1, we aimed to determine if nitrate supplementation (4 mM sodium nitrate via drinking water) improved skeletal muscle mitochondrial bioenergetics and acetylation status in mice fed a high-fat diet (HFD: 60% fat).

CD38-NADase is a new major contributor to Duchenne muscular dystrophic phenotype.

Duchenne muscular dystrophy (DMD) is characterized by progressive muscle degeneration. Two important deleterious features are a Ca dysregulation linked to Ca influxes associated with ryanodine receptor hyperactivation, and a muscular nicotinamide adenine dinucleotide (NAD ) deficit. Here, we identified that deletion in mdx mice of CD38, a NAD glycohydrolase-producing modulators of Ca signaling, led to a fully restored heart function and structure, with skeletal muscle performance improvements, associated with a reduction in inflammation and senescence markers.

Metabolic Therapy of Heart Failure: Is There a Future for B Vitamins?

Heart failure (HF) is a plague of the aging population in industrialized countries that continues to cause many deaths despite intensive research into more effective treatments. Although the therapeutic arsenal to face heart failure has been expanding, the relatively short life expectancy of HF patients is pushing towards novel therapeutic strategies. Heart failure is associated with drastic metabolic disorders, including severe myocardial mitochondrial dysfunction and systemic nutrient deprivation secondary to severe cardiac dysfunction.

Spatiotemporal AMPKα2 deletion in mice induces cardiac dysfunction, fibrosis and cardiolipin remodeling associated with mitochondrial dysfunction in males only.

Background: The AMP-activated protein kinase (AMPK) is a major regulator of cellular energetics which plays key role in acute metabolic response and in long-term adaptation to stress. Recent works have also suggested non-metabolic effects.

Methods: To decipher AMPK roles in the heart, we generated a cardio-specific inducible model of gene deletion of the main cardiac catalytic subunit of AMPK (Ampkα2) in mice.

Insights into the modulation of the interferon response and NAD in the context of COVID-19.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in dramatic worldwide mortality. Along with developing vaccines, the medical profession is exploring new strategies to curb this pandemic. A better understanding of the molecular consequences of SARS-CoV-2 cellular infection could lead to more effective and safer treatments.

NMRK2 Gene Is Upregulated in Dilated Cardiomyopathy and Required for Cardiac Function and NAD Levels during Aging.

Dilated cardiomyopathy (DCM) is a disease of multifactorial etiologies, the risk of which is increased by male sex and age. There are few therapeutic options for patients with DCM who would benefit from identification of common targetable pathways. We used bioinformatics to identify the gene involved in nicotinamide adenine dinucleotde (NAD) coenzyme biosynthesis as activated in different mouse models and in hearts of human patients with DCM while the gene controlling a parallel pathway is repressed.

Nicotinamide adenine dinucleotide: Biosynthesis, consumption and therapeutic role in cardiac diseases.

Nicotinamide adenine dinucleotide (NAD) is an abundant cofactor that plays crucial roles in several cellular processes. NAD can be synthesized de novo starting with tryptophan, or from salvage pathways starting with NAD precursors like nicotinic acid (NA), nicotinamide (NAM) or nicotinamide riboside (NR), referred to as niacin/B vitamins, arising from dietary supply or from cellular NAD catabolism. Given the interconversion between its oxidized (NAD ) and reduced form (NADH), NAD participates in a wide range of reactions: regulation of cellular redox status, energy metabolism and mitochondrial biogenesis.

Blood NAD levels are reduced in very old patients hospitalized for heart failure.

Background: Age-associated decline in nicotinamide adenine dinucleotide (NAD) tissue levels has emerged as potential driving mechanism in the establishment of energy metabolism perturbations in the context of chronic diseases, notably heart failure.

Objective: The aim of this study was to measure the blood NAD levels in a healthy blood donor population and in a population of elderly patients hospitalized for decompensated heart failure.

Method: Whole blood sample was collected from 151 healthy voluntary blood donors, aged 19 to 68 years, and from 19 patients aged 75 to 101 years and hospitalized for decompensated heart failure in a geriatric ward.

Gender issues in cardiovascular diseases. Focus on energy metabolism.

It is increasingly recognized that sex and gender differences (S&G) influence cardiovascular diseases (CVD), greatly impacting disease management. In terms of definition, sex refers to biological aspects, gender effects being mainly related to socio-cultural factors. Both sex and gender are interpenetrated in humans and difficult to separate.

Mechanical and molecular parameters that influence the tendon differentiation potential of C3H10T1/2 cells in 2D- and 3D-culture systems.

One of the main challenges relating to tendons is to understand the regulators of the tendon differentiation program. The optimum culture conditions that favor tendon cell differentiation have not been identified. Mesenchymal stem cells present the ability to differentiate into multiple lineages in cultures under different cues ranging from chemical treatment to physical constraints.

Cardioprotective effects of α-cardiac actin on oxidative stress in a dilated cardiomyopathy mouse model.

The expression of α-cardiac actin, a major constituent of the cytoskeleton of cardiomyocytes, is dramatically decreased in a mouse model of dilated cardiomyopathy triggered by inducible cardiac-specific serum response factor (Srf) gene disruption that could mimic some forms of human dilated cardiomyopathy. To investigate the consequences of the maintenance of α-cardiac actin expression in this model, we developed a new transgenic mouse based on Cre/LoxP strategy, allowing together the induction of SRF loss and a compensatory expression of α-cardiac actin. Here, we report that maintenance of α-cardiac actin within cardiomyocytes temporally preserved cytoarchitecture from adverse cardiac remodeling through a positive impact on both structural and transcriptional levels.

Inducible Cardiac-Specific Deletion of Sirt1 in Male Mice Reveals Progressive Cardiac Dysfunction and Sensitization of the Heart to Pressure Overload.

Heart failure is associated with profound alterations of energy metabolism thought to play a major role in the progression of this syndrome. SIRT1 is a metabolic sensor of cellular energy and exerts essential functions on energy metabolism, oxidative stress response, apoptosis, or aging. Importantly, SIRT1 deacetylates the peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α), the master regulator of energy metabolism involved in mitochondrial biogenesis and fatty acid utilization.

Aged Nicotinamide Riboside Kinase 2 Deficient Mice Present an Altered Response to Endurance Exercise Training.

Skeletal muscle aging is marked by the development of a sarcopenic phenotype, a global decline of muscle energetic capacities, and an intolerance to exercise. Among the metabolic disorders involved in this syndrome, NAD metabolism was shown to be altered in skeletalmuscle, with an important role for the NAMPT enzyme recycling the nicotinamide precursor. An alternative pathway for NAD biosynthesis has been described for the nicotinamide riboside vitamin B3 precursor used by the NMRK kinases, including the striated muscle-specific NMRK2.

Rescue of biosynthesis of nicotinamide adenine dinucleotide protects the heart in cardiomyopathy caused by lamin A/C gene mutation.

Cardiomyopathy caused by lamin A/C gene (LMNA) mutations (hereafter referred as LMNA cardiomyopathy) is an anatomic and pathologic condition associated with muscle and electrical dysfunction of the heart, often leading to heart failure-related disability. There is currently no specific therapy available for patients that target the molecular pathophysiology of LMNA cardiomyopathy. Recent studies suggested that nicotinamide adenine dinucleotide (NAD+) cellular content could be a critical determinant for heart function.