The Impact of the Nervous System on Arteries and the Heart: The Neuroimmune Cardiovascular Circuit Hypothesis

Three systemic biological systems, i.e., the nervous, the immune, and the cardiovascular systems, form a mutually responsive and forward-acting tissue network to regulate acute and chronic cardiovascular function in health and disease. Two sub-circuits within the cardiovascular system have been described, the artery brain circuit (ABC) and the heart brain circuit (HBC), forming a large cardiovascular brain circuit (CBC). Likewise, the nervous system consists of the peripheral nervous system and the central nervous system with their functional distinct sensory and effector arms. Moreover, the immune system with its constituents, i.e., the innate and the adaptive immune systems, interact with the CBC and the nervous system at multiple levels. As understanding the structure and inner workings of the CBC gains momentum, it becomes evident that further research into the CBC may lead to unprecedented classes of therapies to treat cardiovascular diseases as multiple new biologically active molecules are being discovered that likely affect cardiovascular disease progression. Here, we weigh the merits of integrating these recent observations in cardiovascular neurobiology into previous views of cardiovascular disease pathogeneses. These considerations lead us to propose the Neuroimmune Cardiovascular Circuit Hypothesis.