Neural Mechanisms in Cardiovascular Health and Disease

Although the neurocardiac axis is central to cardiovascular homeostasis, its dysregulation drives heart failure and cardiometabolic diseases. This review examines the bidirectional interplay between the autonomic nervous system and the heart, highlighting the role of this interplay in disease progression and its therapeutic potential. The autonomic nervous system modulates cardiac function and vascular tone through its sympathetic and parasympathetic branches. However, in heart failure, chronic sympathetic overdrive and parasympathetic withdrawal exacerbate myocardial remodeling and metabolic dysfunction, both of which are exacerbated by cardiometabolic conditions such as obesity and diabetes. These conditions are increasingly recognized to impair neurocardiac regulation, thereby promoting inflammation and adverse outcomes. An important emerging area concerns neuroimmune control, in which the brain orchestrates systemic inflammation through circuits involving the bone marrow, spleen, and other organs, thereby amplifying cardiovascular damage. This neuroimmune axis integrates peripheral signals to influence immune responses that contribute to disease progression. Lifestyle factors, such as stress, sleep, exercise, and diet, affect autonomic and immune balance and, thus, cardiovascular disease. Therapeutically, targeting neurocardiac and neuroimmune pathways pharmacologically or via neuromodulation (eg, vagal or splenic nerve stimulation) offers promise although the clinical translation of the latter remains challenging. In this review, we synthesize preclinical and clinical data to highlight the neurocardiac axis as a critical nexus in heart failure and cardiometabolic disease. Harnessing neuroimmune and neurocardiac interactions may inform precision approaches to reduce the burden of these conditions.