Autonomic nervous system and cardiac neuro-signaling pathway modulation in cardiovascular disorders and Alzheimer’s disease

Abstract

The heart is a functional syncytium controlled by a delicate and sophisticated balance ensured by the tight coordination of its several cell subpopulations. Accordingly, cardiomyocytes together with the surrounding microenvironment participate in the heart tissue homeostasis. In the right atrium, the sinoatrial nodal cells regulate the cardiac impulse propagation through cardiomyocytes, thus ensuring the maintenance of the electric network in the heart tissue. Notably, the central nervous system (CNS) modulates the cardiac rhythm through the two limbs of the autonomic nervous system (ANS): the parasympathetic and sympathetic compartments. The autonomic nervous system exerts non-voluntary effects on different peripheral organs. The main neuromodulator of the Sympathetic Nervous System (SNS) is norepinephrine, while the principal neurotransmitter of the Parasympathetic Nervous System (PNS) is acetylcholine. Through these two main neurohormones, the ANS can gradually regulate cardiac, vascular, visceral, and glandular functions by turning on one of its two branches (adrenergic and/or cholinergic), which exert opposite effects on targeted organs. Besides these neuromodulators, the cardiac nervous system is ruled by specific neuropeptides (neurotrophic factors) that help to preserve innervation homeostasis through the myocardial layers (from epicardium to endocardium). Interestingly, the dysregulation of this neuro-signaling pathway may expose the cardiac tissue to severe disorders of different etiology and nature. Specifically, a maladaptive remodeling of the cardiac nervous system may culminate in a progressive loss of neurotrophins, thus leading to severe myocardial denervation, as observed in different cardiometabolic and neurodegenerative diseases (myocardial infarction, heart failure, Alzheimer’s disease). This review analyzes the current knowledge on the pathophysiological processes involved in cardiac nervous system impairment from the perspectives of both cardiac disorders and a widely diffused and devastating neurodegenerative disorder, Alzheimer’s disease, proposing a relationship between neurodegeneration, loss of neurotrophic factors, and cardiac nervous system impairment. This overview is conducive to a more comprehensive understanding of the process of cardiac neuro-signaling dysfunction, while bringing to light potential therapeutic scenarios to correct or delay the adverse cardiovascular remodeling, thus improving the cardiac prognosis and quality of life in patients with heart or neurodegenerative disorders.

Cardiopulmonary nerve stimulation as a novel therapy for cardiac autonomic nervous system modulation

“…The malfunctioning CANS is heavily remodeled in cardiac diseases such as myocardial ischemia, myocardial infarction, heart failure, and arrhythmias (Francis and Cohn, 1986 ; Tjeerdsma et al, 2001 ; Campelo and Abreu-Lima, 2004 ; Piepoli and Capucci, 2007 ; Hoyer et al, 2008 ; Kardesoglu et al, 2011 ; Phillips, 2012 ; van Bilsen et al, 2017 ; Ali et al, 2018 ; Hadaya and Ardell, 2020 ; Elia and Fossati, 2023 ; Kumar et al, 2023 ). The CPNS is capable of modulating the entire state of the CANS through both direct and indirect afferent pathway modulation that is transmitted to multiple levels of the CANS.…”

The Recent Applications of PLGA-Based Nanostructures for Ischemic Stroke

“…Neurotrophic factors are critical for neuronal survival as they promote neuronal proliferation, survival, and differentiation [ 117 ]. Neurotrophic factors regulate a variety of neurological activities in ischemic stroke, including neuroprotection [ 118 ], neuroplasticity [ 119 ], and vascular remodeling [ 120 ]. Several studies have shown that neurotrophic factors can be a treatment option for ischemic stroke [ 121 , 122 , 123 ].…”

Advances in cardiac tissue engineering and heart‐on‐a‐chip

“…Endocardial cells, which line the atrial and ventricular chambers, are essential for preserving the heart's inner lining integrity and play a role in the creation of embryonic heart valves 16 . Furthermore, cardiac neurons, which are part of the heart's intrinsic neural system, operate autonomously to control heart rate, rhythm, and contractile force, assuring coordinated cardiac activity 17 . Recent imaging studies, reveal their elaborate positioning intertwined with cardiomyocytes within the myocardium 18 .…”

“…16 Furthermore, cardiac neurons, which are part of the heart's intrinsic neural system, operate autonomously to control heart rate, rhythm, and contractile force, assuring coordinated cardiac activity. 17 Recent imaging studies, reveal their elaborate positioning intertwined with cardiomyocytes within the myocardium. 18 Disregulation of intrinsic cardiac neuron activity can lead to diseases such as arrhythmia and may be one of the causes of loss of cardiac function during ageing.…”