CD38 connects the heart and brain

Cluster of differentiation 38 (CD38) is a widely expressed transmembrane glycoprotein in various human tissues and cells with vital biological roles in the heart and brain, possessing both NADase and cyclase activities. It is involved in regulating heart and brain functions through various pathways, including calcium (Ca2+) signaling nicotinamide adenine dinucleotide (NAD+) content, oxidative stress, inflammation and immune response. Its combined role in heart-brain coexisting diseases suggests that inhibiting CD38 has a protective effect on cardiovascular diseases (CVD) and neurological disorders. This review aims to discuss the expression patterns, regulatory mechanisms, and CD38 signaling pathways in the heart and brain. In conclusion, CD38 is implicated in the shared pathogenesis of heart-brain diseases, providing novel insights for future research.

• Publication year

  2025

• Venue

  Translational Psychiatry

• Publication date

  2025-09-11

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/s41398-025-03597-9PMID 40935818PMCID 12426220
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Heart-brain axis: pushing the boundaries of cardiovascular molecular imaging.

  2024cited by this paper
• The role of CD38 in inflammation-induced depression-like behavior and the antidepressant effect of (R)-ketamine.

  2023cited by this paper
• Multiple Sclerosis Is Associated with Immunoglobulin Germline Gene Variation of Transitional B Cells

  2023cited by this paper
• Effects of Apocynin, a NADPH Oxidase Inhibitor, in the Protection of the Heart from Ischemia/Reperfusion Injury

  2023cited by this paper
• Cardiovascular Brain Circuits

  2023cited by this paper
• NAD+ exhaustion by CD38 upregulation contributes to blood pressure elevation and vascular damage in hypertension

  2023cited by this paper
• The etiology of poststroke-depression: a hypothesis involving HPA axis.

  2022cited by this paper
• Benefits in cardiac function by CD38 suppression: Improvement in NAD+ levels, exercise capacity, heart rate variability and protection against catecholamine induced ventricular arrhythmias.

  2022cited by this paper
• Amyloidosis in Alzheimer’s Disease: Pathogeny, Etiology, and Related Therapeutic Directions

  2022cited by this paper
• Novel therapies for treatment of antibody-mediated rejection of the kidney

  2022cited by this paper
• Aβ promotes CD38 expression in senescent microglia in Alzheimer’s disease

  2022cited by this paper
• Niacin promotes the efflux of lysosomal cholesterol from macrophages via the CD38/NAADP signaling pathway

  2022cited by this paper
• Recent advances in the pharmacological therapy of chronic heart failure: Evidence and guidelines.

  2022cited by this paper
• Anti CD38 monoclonal antibodies for multiple myeloma treatment

  2022cited by this paper
• Immunoglobulin light chain amyloidosis: 2022 update on diagnosis, prognosis, and treatment

  2022cited by this paper
• Influence of Carbon Support Structure on Cathode Catalysts Durability the Authors Declare No Competing Interests

  2022cited by this paper
• NAD+ metabolism drives astrocyte proinflammatory reprogramming in central nervous system autoimmunity

  2022cited by this paper
• Daratumumab in amyloidosis.

  2022cited by this paper
• Orally Bioavailable Enzymatic Inhibitor of CD38, MK-0159, Protects against Ischemia/Reperfusion Injury in the Murine Heart.

  2022cited by this paper
• Characterizing CD38 Expression and Enzymatic Activity in the Brain of Spontaneously Hypertensive Stroke-Prone Rats

  2022influential reference
• Non-sustained ventricular tachycardia due to extreme road traffic stress in a healthy adult.

  2022cited by this paper
• Publisher Correction: Reappraising the role of inflammation in heart failure

  2021cited by this paper
• Cognitive impairment in myocardial infarction and heart failure

  2021cited by this paper
• Mechanism and therapeutic strategies of depression after myocardial infarction

  2021cited by this paper
• NAD+ and Cardiovascular Diseases.

  2021cited by this paper
• Critical Role of Astrocyte NAD+ Glycohydrolase in Myelin Injury and Regeneration

  2021cited by this paper
• CD38 and MGluR1 as possible signaling molecules involved in epileptogenesis: a potential role for NAD+ homeostasis.

  2021cited by this paper
• Peripheral blood lymphocyte phenotypes in Alzheimer and Parkinson's diseases.

  2021cited by this paper
• Optimising cardiovascular care of patients with multiple myeloma

  2021cited by this paper
• Inhibition of CD38 and supplementation of nicotinamide riboside ameliorate lipopolysaccharide‐induced microglial and astrocytic neuroinflammation by increasing NAD+

  2021cited by this paper
• Cerebral blood flow impairment and cognitive decline in heart failure

  2021cited by this paper
• Diversity among Differentially Expressed Genes in Atrial Appendages of Atrial Fibrillation: The Role and Mechanism of SPP1 in Atrial Fibrosis.

  2021cited by this paper
• Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis.

  2021cited by this paper
• CD38 deficiency alleviates Ang II-induced vascular remodeling by inhibiting small extracellular vesicle-mediated vascular smooth muscle cell senescence in mice

  2021cited by this paper
• Defective CD19+CD24hiCD38hi transitional B-cell function in patients with relapsing-remitting MS

  2020cited by this paper
• Preliminary Evidence That CD38 Moderates the Association of Neuroticism on Amygdala-Subgenual Cingulate Connectivity

  2020cited by this paper
• Cardiac Amyloidosis: Overlooked, Underappreciated, and Treatable.

  2020cited by this paper
• CD38 in Neurodegeneration and Neuroinflammation

  2020cited by this paper
• Inflammation in Heart Failure: JACC State-of-the-Art Review.

  2020cited by this paper
• CD38 Causes Autophagic Flux Inhibition and Cardiac Dysfunction Through a Transcriptional Inhibition Pathway Under Hypoxia/Ischemia Conditions

  2020cited by this paper
• A Novel Role of CD38 and Oxytocin as Tandem Molecular Moderators of Human Social Behavior.

  2020cited by this paper
• Regulation of NLRP3 inflammasome by CD38 through cADPR-mediated Ca2+ release in vascular smooth muscle cells in diabetic mice.

  2020cited by this paper
• Activation of astrocytic sigma‐1 receptor exerts antidepressant‐like effect via facilitating CD38‐driven mitochondria transfer

  2020cited by this paper
• CD38: A Potential Therapeutic Target in Cardiovascular Disease

  2020cited by this paper
• Metabolic Inflammation in Heart Failure with Preserved Ejection Fraction.

  2020cited by this paper
• CD38: T Cell Immuno-Metabolic Modulator

  2020cited by this paper
• Isatuximab for the treatment of relapsed/refractory multiple myeloma

  2020cited by this paper
• In vivo evaluation of CD38 and CD138 as targets for nanoparticle-based drug delivery in multiple myeloma

  2020cited by this paper
• CD38: An Immunomodulatory Molecule in Inflammation and Autoimmunity

  2020cited by this paper
• Case Report: Daratumumab in a Patient With Severe Refractory Anti-NMDA Receptor Encephalitis

  2020cited by this paper
• A multiscale analysis in CD38−/− mice unveils major prefrontal cortex dysfunctions

  2019cited by this paper
• Peripheral blood lymphocyte phenotypes in Alzheimer and Parkinson's diseases.

  2019cited by this paper
• The Role of Depressive Subtypes within the Neuroinflammation Hypothesis of Major Depressive Disorder.

  2019cited by this paper
• Inhibition of CD38 with the Thiazoloquin(az)olin(on)e 78c Protects the Heart against Postischemic Injury

  2019cited by this paper
• Oxytocin pathway gene networks in the human brain

  2019cited by this paper
• Management of cardiovascular risk in patients with multiple myeloma

  2019cited by this paper
• Heart failure with preserved ejection fraction, atrial fibrillation, and the role of senile amyloidosis

  2019cited by this paper
• CD38 Deficiency Protects Heart from High Fat Diet-Induced Oxidative Stress Via Activating Sirt3/FOXO3 Pathway

  2018cited by this paper
• The Lancet Commission on global mental health and sustainable development.

  2018cited by this paper
• Hippocampal CA1 βCaMKII mediates neuroinflammatory responses via COX-2/PGE2 signaling pathways in depression

  2018cited by this paper
• Case Report: Treatment of light‐chain amyloidosis with daratumumab monotherapy in two patients

  2018cited by this paper
• Vitamin A Deficiency Induces Autistic‐Like Behaviors in Rats by Regulating the RAR&bgr;‐CD38‐Oxytocin Axis in the Hypothalamus

  2018cited by this paper
• Inhibiting the CD38/cADPR pathway protected rats against sepsis associated brain injury.

  2018cited by this paper
• Characterization of CD38 in the major cell types of the heart: endothelial cells highly express CD38 with activation by hypoxia-reoxygenation triggering NAD(P)H depletion.

  2018cited by this paper
• Additional Information.

  2018cited by this paper
• Circulating T-Cell Subsets, Monocytes, and Natural Killer Cells in Peripartum Cardiomyopathy: Results From the Multicenter IPAC Study.

  2018cited by this paper
• Inactivation of Serotonergic Neurons in the Rostral Medullary Raphé Attenuates Stress-Induced Tachypnea and Tachycardia in Mice

  2018cited by this paper
• Protective Role of Autophagy in Nlrp3 Inflammasome Activation and Medial Thickening of Mouse Coronary Arteries.

  2018cited by this paper
• The role of 5-HT receptors in depression

  2017cited by this paper
• Calcium Signaling and Cardiac Arrhythmias.

  2017cited by this paper
• CD38 promotes angiotensin II‐induced cardiac hypertrophy

  2017cited by this paper
• The role of 5-HT receptors in depression

  2017cited by this paper
• Luteolinidin Protects the Postischemic Heart through CD38 Inhibition with Preservation of NAD(P)(H)

  2017influential reference
• Protein Misfolding, Amyloid Formation, and Human Disease: A Summary of Progress Over the Last Decade.

  2017cited by this paper
• Protective Role of Autophagy in NLRP3 Inflammasome Activation and Medial Thickening of Mouse Coronary Arteries

  2017cited by this paper
• Role of the immune system in cardiac tissue damage and repair following myocardial infarction

  2017cited by this paper
• Daratumumab for the treatment of multiple myeloma

  2017cited by this paper
• Cardiovascular complications of multiple myeloma in the elderly

  2017cited by this paper
• Depression and Heart Diseases: Leading Health Problems.

  2017cited by this paper
• Implication of CD38 gene in autophagic degradation of collagen I in mouse coronary arterial myocytes.

  2017cited by this paper
• Lysosomal cholesterol accumulation in macrophages leading to coronary atherosclerosis in CD38−/− mice

  2016cited by this paper
• CD38 Deficiency Protects the Heart from Ischemia/Reperfusion Injury through Activating SIRT1/FOXOs-Mediated Antioxidative Stress Pathway

  2016cited by this paper
• Daratumumab: First Global Approval

  2016cited by this paper
• Interaction of CD38 Variant and Chronic Interpersonal Stress Prospectively Predicts Social Anxiety and Depression Symptoms Over 6 Years

  2016cited by this paper
• CD38 Knockout Mice Show Significant Protection Against Ischemic Brain Damage Despite High Level Poly-ADP-Ribosylation

  2016cited by this paper
• Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis.

  2016cited by this paper
• Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis

  2016cited by this paper
• CD38 Knockout Mice Show Significant Protection Against Ischemic Brain Damage Despite High Level Poly-ADP-Ribosylation

  2016cited by this paper
• Evolving therapies for myocardial ischemia/reperfusion injury.

  2015cited by this paper
• Contribution of Nrf2 to Atherogenic Phenotype Switching of Coronary Arterial Smooth Muscle Cells Lacking CD38 Gene

  2015cited by this paper
• Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy.

  2015cited by this paper
• Depletion of NADP(H) due to CD38 activation triggers endothelial dysfunction in the postischemic heart

  2015influential reference
• Alzheimer's disease pathology is attenuated in a CD38‐deficient mouse model

  2015cited by this paper
• Depression and cardiovascular disease: a clinical review.

  2014influential reference
• Cognitive impairment and cardiovascular diseases in the elderly. A heart-brain continuum hypothesis.

  2014cited by this paper
• Defective autophagosome trafficking contributes to impaired autophagic flux in coronary arterial myocytes lacking CD38 gene.

  2014cited by this paper
• Design, Synthesis and SAR Studies of NAD Analogues as Potent Inhibitors towards CD38 NADase

  2014cited by this paper
• Myocardial ischemia-reperfusion injury: a neglected therapeutic target.

  2013cited by this paper
• The effects of apoptosis vulnerability markers on the myocardium in depression after myocardial infarction

  2013cited by this paper
• Integrative neurochemistry and neurobiology of social recognition and behavior analyzed with respect to CD38-dependent brain oxytocin secretion.

  2013cited by this paper

• No citing papers are available for this paper.