The Role of Oxytocin in Cardiovascular Protection

Jankowski, Marek; Broderick, Tom L.; Gutkowska, Jolanta

doi:10.3389/fpsyg.2020.02139

Cited by 66 publications

(55 citation statements)

References 154 publications

(266 reference statements)

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“…As OT has pleiotropic effects, the therapeutic perspectives are truly exciting. Indeed, OT has broad implications for general health: OT is a stress-coping molecule with anti-inflammatory and antioxidant properties; influences the immune system, body composition, cognitive functions and mood; and has been tested in the treatment of numerous diseases, including anxiety, pain, diabetes, cardiovascular diseases and breast cancer [1,27,[40][41][42][43][44][45].…”

Section: Oxytocin As a Therapeutic Agent: Perspectivesmentioning

confidence: 99%

Oxytocin and Bone: Review and Perspectives

Breuil

Trojani

Amri

2021

IJMS

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Recent data demonstrate the anabolic effect of oxytocin on bone. Bone cells express oxytocin receptors. Oxytocin promotes osteoblasts differentiation and function, leading to an increased bone formation with no effect on bone resorption and an improvement of bone microarchitecture. Oxytocin is synthetized by osteoblasts, and this synthesis is stimulated by estrogen. Animal studies demonstrate a direct action of oxytocin on bone, as the systemic administration of oxytocin prevents and reverses the bone loss induced by estrogen deficiency. Although oxytocin is involved in bone formation in both sexes during development, oxytocin treatment has no effect on male osteoporosis, underlining the importance of estrogen that amplifies its local autocrine and paracrine secretion. There are few human data showing a decrease in the oxytocin serum level in anorexia nervosa independently of estrogen and in amenorrheic women associated with impaired bone microarchitecture; in post-menopausal women a higher oxytocin serum level is associated with higher bone density, but not in osteoporotic men. Oxytocin displays many effects that may be beneficial in the management of osteoporosis, cardiovascular diseases, cognitive disorders, breast cancer, diabetes and body fat gain, all age-related diseases affecting elderly women, opening exciting therapeutic perspectives, although the issue is to find a single route, dosage and schedule able to reach all these targets.

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Section: Oxytocin As a Therapeutic Agent: Perspectivesmentioning

confidence: 99%

Oxytocin and Bone: Review and Perspectives

Breuil

Trojani

Amri

2021

IJMS

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“…These signal pathways have been implicated in processes thought to underlie smooth muscle contraction and NO production. These signal pathways leading to functions that result in a reduction of heart rate and contraction, and vasodilation are reportedly regulated by actions of ANP-guanosine-3′,5′-cyclic monophosphate (cGMP), and NO-cGMP systems [ 15 ]. Therefore, molecular signaling of OT in the heart is estimated to be largely dependent on the Gq/11 protein and its downstream targets.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, maternal blood pressure during pregnancy does not correspond to the action of OT through Gq/11-IP 3 -dependent elevation of intracellular Ca 2+ concentration. Although serum circulating OT is believed to prevent hypertension, and to be cardioprotective by reducing the inflammatory response and improving cardiovascular function [ 15 ], signaling pathway of OT through Gq/11-IP 3 -dependent activation of PKC and IP 3 may not be appropriate enough to illustrate the beneficial effect of OT in the cardiovascular system. In this context, downregulation of the Cav1.2 channel in cardiomyocytes, as shown in this study and possibly in vascular smooth muscle cells, may account for beneficial action of OT in cardioprotection and control of blood pressure during pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Oxytocin Downregulates the CaV1.2 L-Type Ca2+ Channel via Gi/cAMP/PKA/CREB Signaling Pathway in Cardiomyocytes

et al. 2021

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Oxytocin (OT) and its receptor (OTR) are expressed in the heart and are involved in the physiological cardiovascular functional system. Although it is known that OT/OTR signaling is cardioprotective by reducing the inflammatory response and improving cardiovascular function, the role of OT in the cardiac electrical excitation modulation has not been clarified. This study investigates the molecular mechanism of the action of OT on cardiomyocyte membrane excitation focusing on the L-type Ca2+ channel. Our methodology uses molecular biological methods and a patch-clamp technique on rat cardiomyocytes with OT, combined with several signal inhibitors and/or activators. Our results show that long-term treatment of OT significantly decreases the expression of Cav1.2 mRNA, and reduces the L-type Ca2+ channel current (ICa.L) in cardiomyocytes. OT downregulates the phosphorylated component of a transcription factor adenosine-3′,5′-cyclic monophosphate (cAMP) response element binding protein (CREB), whose action is blocked by OTR antagonist and pertussis toxin, a specific inhibitor of the inhibitory GTP-binding regulators of adenylate cyclase, Gi. On the other hand, the upregulation of Cav1.2 mRNA expression by isoproterenol is halted by OT. Furthermore, inhibition of phospholipase C (PLC) was without effect on the OT action to downregulate Cav1.2 mRNA—which suggests a signal pathway of Gi/protein kinase A (PKA)/CREB mediated by OT/OTR. These findings indicate novel signaling pathways of OT contributing to a downregulation of the Cav1.2-L-type Ca2+ channel in cardiomyocytes.

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“…The OXTR can also be found abundantly in cardiomyocytes, where it exerts cardioprotective effects through different signaling pathways. These include deceleration of atherosclerosis, protection from myocardial metabolic and inflammatory injury, as well as post-ischemia repair [ 106 , 107 ].…”

Section: The Oxytocin Receptor In the Periphery—expression In Key Metabolic Organsmentioning

confidence: 99%

The Effects of Oxytocin on Appetite Regulation, Food Intake and Metabolism in Humans

Kerem

Lawson

2021

IJMS

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The hypothalamic peptide oxytocin and its receptor are involved in a range of physiological processes, including parturition, lactation, cell growth, wound healing, and social behavior. More recently, increasing evidence has established the effects of oxytocin on food intake, energy expenditure, and peripheral metabolism. In this review, we provide a comprehensive description of the central oxytocinergic system in which oxytocin acts to shape eating behavior and metabolism. Next, we discuss the peripheral beneficial effects oxytocin exerts on key metabolic organs, including suppression of visceral adipose tissue inflammation, skeletal muscle regeneration, and bone tissue mineralization. A brief summary of oxytocin actions learned from animal models is presented, showing that weight loss induced by chronic oxytocin treatment is related not only to its anorexigenic effects, but also to the resulting increase in energy expenditure and lipolysis. Following an in-depth discussion on the technical challenges related to endogenous oxytocin measurements in humans, we synthesize data related to the association between endogenous oxytocin levels, weight status, metabolic syndrome, and bone health. We then review clinical trials showing that in humans, acute oxytocin administration reduces food intake, attenuates fMRI activation of food motivation brain areas, and increases activation of self-control brain regions. Further strengthening the role of oxytocin in appetite regulation, we review conditions of hypothalamic insult and certain genetic pathologies associated with oxytocin depletion that present with hyperphagia, extreme weight gain, and poor metabolic profile. Intranasal oxytocin is currently being evaluated in human clinical trials to learn whether oxytocin-based therapeutics can be used to treat obesity and its associated sequela. At the end of this review, we address the fundamental challenges that remain in translating this line of research to clinical care.

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The Role of Oxytocin in Cardiovascular Protection

Cited by 66 publications

References 154 publications

Oxytocin and Bone: Review and Perspectives

Oxytocin and Bone: Review and Perspectives

Oxytocin Downregulates the CaV1.2 L-Type Ca2+ Channel via Gi/cAMP/PKA/CREB Signaling Pathway in Cardiomyocytes

The Effects of Oxytocin on Appetite Regulation, Food Intake and Metabolism in Humans

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