scholarly journals Therapeutic Potential of Emerging NAD+-Increasing Strategies for Cardiovascular Diseases

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1939
Author(s):  
Noemi Rotllan ◽  
Mercedes Camacho ◽  
Mireia Tondo ◽  
Elena M. G. Diarte-Añazco ◽  
Marina Canyelles ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Nicotinamide Adenine Dinucleotide ◽  
Therapeutic Potential ◽  
Metabolic Stress ◽  
Therapeutic Strategies ◽  
Experimental Models ◽  
Vascular Health ◽  
Nad Metabolism ◽  
Pathological Conditions ◽  
Mammalian Tissues

Cardiovascular diseases are the leading cause of death worldwide. Aging and/or metabolic stress directly impact the cardiovascular system. Over the last few years, the contributions of altered nicotinamide adenine dinucleotide (NAD+) metabolism to aging and other pathological conditions closely related to cardiovascular diseases have been intensively investigated. NAD+ bioavailability decreases with age and cardiometabolic conditions in several mammalian tissues. Compelling data suggest that declining tissue NAD+ is commonly related to mitochondrial dysfunction and might be considered as a therapeutic target. Thus, NAD+ replenishment by either genetic or natural dietary NAD+-increasing strategies has been recently demonstrated to be effective for improving the pathophysiology of cardiac and vascular health in different experimental models, as well as human health, to a lesser extent. Here, we review and discuss recent experimental evidence illustrating that increasing NAD+ bioavailability, particularly by the use of natural NAD+ precursors, may offer hope for new therapeutic strategies to prevent and treat cardiovascular diseases.

scholarly journals Identification of evolutionary and kinetic drivers of NAD-dependent signaling

2019 ◽  
Vol 116 (32) ◽  
pp. 15957-15966 ◽  
Author(s):  
Mathias Bockwoldt ◽  
Dorothée Houry ◽  
Marc Niere ◽  
Toni I. Gossmann ◽  
Ines Reinartz ◽  
...  
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Phylogenetic Analyses ◽  
Adenosine Diphosphate ◽  
Therapeutic Strategies ◽  
Structural Adaptation ◽  
Disease Treatment ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Nad Metabolism ◽  
High Affinity ◽  
Cellular Events

Nicotinamide adenine dinucleotide (NAD) provides an important link between metabolism and signal transduction and has emerged as central hub between bioenergetics and all major cellular events. NAD-dependent signaling (e.g., by sirtuins and poly–adenosine diphosphate [ADP] ribose polymerases [PARPs]) consumes considerable amounts of NAD. To maintain physiological functions, NAD consumption and biosynthesis need to be carefully balanced. Using extensive phylogenetic analyses, mathematical modeling of NAD metabolism, and experimental verification, we show that the diversification of NAD-dependent signaling in vertebrates depended on 3 critical evolutionary events: 1) the transition of NAD biosynthesis to exclusive usage of nicotinamide phosphoribosyltransferase (NamPT); 2) the occurrence of nicotinamide N-methyltransferase (NNMT), which diverts nicotinamide (Nam) from recycling into NAD, preventing Nam accumulation and inhibition of NAD-dependent signaling reactions; and 3) structural adaptation of NamPT, providing an unusually high affinity toward Nam, necessary to maintain NAD levels. Our results reveal an unexpected coevolution and kinetic interplay between NNMT and NamPT that enables extensive NAD signaling. This has implications for therapeutic strategies of NAD supplementation and the use of NNMT or NamPT inhibitors in disease treatment.

scholarly journals Therapeutic Potential of Stem Cells Strategy for Cardiovascular Diseases

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Chang Youn Lee ◽  
Ran Kim ◽  
Onju Ham ◽  
Jihyun Lee ◽  
Pilseog Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cardiovascular Diseases ◽  
Therapeutic Potential ◽  
Therapeutic Strategies ◽  
Paracrine Effects ◽  
Mortality And Morbidity ◽  
The Past ◽  
Cell Based Therapy ◽  
Immunomodulatory Capacity

Despite development of medicine, cardiovascular diseases (CVDs) are still the leading cause of mortality and morbidity worldwide. Over the past 10 years, various stem cells have been utilized in therapeutic strategies for the treatment of CVDs. CVDs are characterized by a broad range of pathological reactions including inflammation, necrosis, hyperplasia, and hypertrophy. However, the causes of CVDs are still unclear. While there is a limit to the currently available target-dependent treatments, the therapeutic potential of stem cells is very attractive for the treatment of CVDs because of their paracrine effects, anti-inflammatory activity, and immunomodulatory capacity. Various studies have recently reported increased therapeutic potential of transplantation of microRNA- (miRNA-) overexpressing stem cells or small-molecule-treated cells. In addition to treatment with drugs or overexpressed miRNA in stem cells, stem cell-derived extracellular vesicles also have therapeutic potential because they can deliver the stem cell-specific RNA and protein into the host cell, thereby improving cell viability. Here, we reported the state of stem cell-based therapy for the treatment of CVDs and the potential for cell-free based therapy.

scholarly journals Exploring the Potential Role of the Gut Microbiome in Chemotherapy-Induced Neurocognitive Disorders and Cardiovascular Toxicity

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 782
Author(s):  
Sona Ciernikova ◽  
Michal Mego ◽  
Michal Chovanec
Keyword(s):  
Cardiovascular Diseases ◽  
Cancer Survivors ◽  
Cancer Patients ◽  
Gut Microbiome ◽  
Late Effects ◽  
Fecal Microbiota Transplantation ◽  
Experimental Models ◽  
Neurocognitive Disorders ◽  
Cardiovascular Toxicity

Chemotherapy, targeting not only malignant but also healthy cells, causes many undesirable side effects in cancer patients. Due to this fact, long-term cancer survivors often suffer from late effects, including cognitive impairment and cardiovascular toxicity. Chemotherapy damages the intestinal mucosa and heavily disrupts the gut ecosystem, leading to gastrointestinal toxicity. Animal models and clinical studies have revealed the associations between intestinal dysbiosis and depression, anxiety, pain, impaired cognitive functions, and cardiovascular diseases. Recently, a possible link between chemotherapy-induced gut microbiota disruption and late effects in cancer survivors has been proposed. In this review, we summarize the current understanding of preclinical and clinical findings regarding the emerging role of the microbiome and the microbiota–gut–brain axis in chemotherapy-related late effects affecting the central nervous system (CNS) and heart functions. Importantly, we provide an overview of clinical trials evaluating the relationship between the gut microbiome and cancer survivorship. Moreover, the beneficial effects of probiotics in experimental models and non-cancer patients with neurocognitive disorders and cardiovascular diseases as well as several studies on microbiota modulations via probiotics or fecal microbiota transplantation in cancer patients are discussed.

scholarly journals GT-Repeat Polymorphism in the HO-1 Gene Promoter Is Associated with Risk of Liver Cancer: A Follow-Up Study from Arseniasis-Endemic Areas in Taiwan

2021 ◽  
Vol 10 (7) ◽  
pp. 1489
Author(s):  
Meei-Maan Wu ◽  
Fang-I Hsieh ◽  
Ling-I Hsu ◽  
Te-Chang Lee ◽  
Hung-Yi Chiou ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cancer Risk ◽  
Cox Regression ◽  
Therapeutic Potential ◽  
Gene Promoter ◽  
Experimental Models ◽  
Heme Oxygenase 1 ◽  
Cox Regression Analysis ◽  
S Alleles

The induction of heme oxygenase-1 (HO-1) has been shown to have therapeutic potential in experimental models of hepatitis and liver fibrosis, which are closely related to liver cancer. In humans, HO-1 induction is transcriptionally modulated by the length of a GT-repeat [(GT)n] in the promoter region. We aimed to investigate the effect of HO-1 (GT)n variants on liver cancer in a human population. We determined the HO-1 genotype in 1153 study subjects and examined their association with liver cancer risk during a 15.9-year follow-up. Allelic polymorphisms were classified as short [S, <27 (GT)n] or long [L, ≥27 (GT)n]. Newly developed cancer cases were identified through linkage to the National Cancer Registry of Taiwan. Multivariate Cox regression analysis was used to evaluate the effect of the HO-1 (GT)n variants. Alpha-fetoprotein (AFP) and cirrhosis history were also examined. The S/S genotype was found to be significantly associated with liver cancer risk, compared to the L/S and L/L genotypes. The S/S genotype group also had a higher percentage of subjects with abnormal AFP levels than other groups. There were significant percentages of cirrhosis among groups who carried S-alleles. Our findings indicate that short (GT)n variants in the HO-1 gene may confer susceptibility to rather than protection from liver cirrhosis/cancer.

scholarly journals A paradigm shift in cell-free approach: the emerging role of MSCs-derived exosomes in regenerative medicine

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Soudeh Moghadasi ◽  
Marischa Elveny ◽  
Heshu Sulaiman Rahman ◽  
Wanich Suksatan ◽  
Abduladheem Turki Jalil ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Ethical Issues ◽  
Therapeutic Potential ◽  
Kidney Diseases ◽  
Experimental Models ◽  
Live Cells ◽  
Target Cells ◽  
Intercellular Interaction ◽  
Micro Rnas

AbstractRecently, mesenchymal stem/stromal cells (MSCs) due to their pro-angiogenic, anti-apoptotic, and immunoregulatory competencies along with fewer ethical issues are presented as a rational strategy for regenerative medicine. Current reports have signified that the pleiotropic effects of MSCs are not related to their differentiation potentials, but rather are exerted through the release of soluble paracrine molecules. Being nano-sized, non-toxic, biocompatible, barely immunogenic, and owning targeting capability and organotropism, exosomes are considered nanocarriers for their possible use in diagnosis and therapy. Exosomes convey functional molecules such as long non-coding RNAs (lncRNAs) and micro-RNAs (miRNAs), proteins (e.g., chemokine and cytokine), and lipids from MSCs to the target cells. They participate in intercellular interaction procedures and enable the repair of damaged or diseased tissues and organs. Findings have evidenced that exosomes alone are liable for the beneficial influences of MSCs in a myriad of experimental models, suggesting that MSC- exosomes can be utilized to establish a novel cell-free therapeutic strategy for the treatment of varied human disorders, encompassing myocardial infarction (MI), CNS-related disorders, musculoskeletal disorders (e.g. arthritis), kidney diseases, liver diseases, lung diseases, as well as cutaneous wounds. Importantly, compared with MSCs, MSC- exosomes serve more steady entities and reduced safety risks concerning the injection of live cells, such as microvasculature occlusion risk. In the current review, we will discuss the therapeutic potential of MSC- exosomes as an innovative approach in the context of regenerative medicine and highlight the recent knowledge on MSC- exosomes in translational medicine, focusing on in vivo researches.

scholarly journals Pathogen induced subversion of NAD+ metabolism mediating host cell death: a target for development of chemotherapeutics

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ayushi Chaurasiya ◽  
Swati Garg ◽  
Ashish Khanna ◽  
Chintam Narayana ◽  
Ved Prakash Dwivedi ◽  
...  
Keyword(s):  
Cell Death ◽  
Host Cell ◽  
Nicotinamide Adenine Dinucleotide ◽  
Malaria Parasite ◽  
Host Cells ◽  
Nicotinamide Adenine ◽  
Targeted Therapeutics ◽  
Nad Metabolism ◽  
Host Cell Death ◽  
Nanomolar Range

AbstractHijacking of host metabolic status by a pathogen for its regulated dissemination from the host is prerequisite for the propagation of infection. M. tuberculosis secretes an NAD+-glycohydrolase, TNT, to induce host necroptosis by hydrolyzing Nicotinamide adenine dinucleotide (NAD+). Herein, we expressed TNT in macrophages and erythrocytes; the host cells for M. tuberculosis and the malaria parasite respectively, and found that it reduced the NAD+ levels and thereby induced necroptosis and eryptosis resulting in premature dissemination of pathogen. Targeting TNT in M. tuberculosis or induced eryptosis in malaria parasite interferes with pathogen dissemination and reduction in the propagation of infection. Building upon our discovery that inhibition of pathogen-mediated host NAD+ modulation is a way forward for regulation of infection, we synthesized and screened some novel compounds that showed inhibition of NAD+-glycohydrolase activity and pathogen infection in the nanomolar range. Overall this study highlights the fundamental importance of pathogen-mediated modulation of host NAD+ homeostasis for its infection propagation and novel inhibitors as leads for host-targeted therapeutics.

scholarly journals Therapeutic Features and Updated Clinical Trials of Mesenchymal Stem Cell (MSC)-Derived Exosomes

2021 ◽  
Vol 10 (4) ◽  
pp. 711
Author(s):  
Byung-Chul Lee ◽  
Insung Kang ◽  
Kyung-Rok Yu
Keyword(s):  
Clinical Trials ◽  
Therapeutic Agent ◽  
Therapeutic Potential ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Genetic Material ◽  
Experimental Models ◽  
Attractive Alternative ◽  
Cell Based Therapy ◽  
Cellular Rejection

Identification of the immunomodulatory and regenerative properties of mesenchymal stem cells (MSCs) have made them an attractive alternative therapeutic option for diseases with no effective treatment options. Numerous clinical trials have followed; however, issues such as infusional toxicity and cellular rejection have been reported. To address these problems associated with cell-based therapy, MSC exosome therapy was developed and has shown promising clinical outcomes. MSC exosomes are nanosized vesicles secreted from MSCs and represent a non-cellular therapeutic agent. MSC exosomes retain therapeutic features of the cells from which they originated including genetic material, lipids, and proteins. Similar to MSCs, exosomes can induce cell differentiation, immunoregulation, angiogenesis, and tumor suppression. MSC exosomes have therefore been employed in several experimental models and clinical studies. Here, we review the therapeutic potential of MSC-derived exosomes and summarize currently ongoing clinical trials according to disease type. In addition, we propose several functional enhancement strategies for the effective clinical application of MSC exosome therapy.

scholarly journals Circadian Deregulation as Possible New Player in Pollution-Induced Tissue Damage

Atmosphere ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 116
Author(s):  
Mascia Benedusi ◽  
Elena Frigato ◽  
Cristiano Bertolucci ◽  
Giuseppe Valacchi
Keyword(s):  
Cardiovascular Diseases ◽  
Air Pollutants ◽  
Environmental Stressors ◽  
Common Mechanism ◽  
Particulate Matters ◽  
Circadian Misalignment ◽  
Pathological Conditions ◽  
Peripheral Clocks ◽  
Living Organisms ◽  
Almost All

Circadian rhythms are 24-h oscillations driven by a hypothalamic master oscillator that entrains peripheral clocks in almost all cells, tissues and organs. Circadian misalignment, triggered by industrialization and modern lifestyles, has been linked to several pathological conditions, with possible impairment of the quality or even the very existence of life. Living organisms are continuously exposed to air pollutants, and among them, ozone or particulate matters (PMs) are considered to be among the most toxic to human health. In particular, exposure to environmental stressors may result not only in pulmonary and cardiovascular diseases, but, as it has been demonstrated in the last two decades, the skin can also be affected by pollution. In this context, we hypothesize that chronodistruption can exacerbate cell vulnerability to exogenous damaging agents, and we suggest a possible common mechanism of action in deregulation of the homeostasis of the pulmonary, cardiovascular and cutaneous tissues and in its involvement in the development of pathological conditions.

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