Pleiotropic activity of nerve growth factor in regulating cardiac functions and counteracting pathogenesis

Abstract

Cardiac innervation density generally reflects the levels of nerve growth factor (NGF) produced by the heart-changes in NGF expression within the heart and vasculature contribute to neuronal remodelling (e.g. sympathetic hyperinnervation or denervation). Its synthesis and release are altered under different pathological conditions. Although NGF is well known for its survival effects on neurons, it is clear that these effects are more wide ranging. Recent studies reported both in vitro and in vivo evidence for beneficial actions of NGF on cardiomyocytes in normal and pathological hearts, including prosurvival and antiapoptotic effects. NGF also plays an important role in the crosstalk between the nervous and cardiovascular systems. It was the first neurotrophin to be implicated in postnatal angiogenesis and vasculogenesis by autocrine and paracrine mechanisms. In connection with these unique cardiovascular properties of NGF, we have provided comprehensive insight into its function and potential effect of NGF underlying heart sustainable/failure conditions. This review aims to summarize the recent data on the effects of NGF on various cardiovascular neuronal and non-neuronal functions. Understanding these mechanisms with respect to the diversity of NGF functions may be crucial for developing novel therapeutic strategies, including NGF action mechanism-guided therapies.

Do Neurotrophins Connect Neurological Disorders and Heart Diseases?

“…NGF is expressed in the normal heart, as shown in Table 1 and [ 34 ], but its synthesis and release are altered under various pathological conditions [ 10 , 11 , 12 , 13 ]. NGF is an important factor in myocardial response to ischemia.…”

“…In severe heart failure, continuous norepinephrine infusion induces a loss of sympathetic fibers, presumably because of NGF reduction [ 71 ]. Taken together, although NTs are involved in the pathophysiology of heart failure, it remains unclear whether CNS disorders are caused by autonomic nervous system hyperactivation as described below [ 13 , 23 , 24 ] ( Figure 2 ).…”

“…Although NTs are the most characterized trophic factors in the peripheral and central nervous systems, recently emerged, strong evidence suggests that NTs play important roles in cardiovascular systems [ 10 , 11 , 12 , 13 ]. In the early embryonic developmental stage, NTs, particularly BDNF, NT-3, and TrkB, and NT receptors are required in order to form a normal heart and vascular system [ 14 , 15 , 16 , 17 ].…”

“…In addition to their function in controlling heart and vascular development, NTs regulate the innervation of sympathetic, parasympathetic, and sensory neurons during development [ 1 , 2 , 3 ]. NTs play an important role in regulating the autonomic and sensory nervous systems, acting not only as trophic survival factors, but also as regulators of cardiac nerve outgrowth and arborization [ 10 , 11 , 12 , 13 ], as well as musculoskeletal regulation [ 18 ].…”

“…On the one hand, how the heart influences the brain via NTs has been relatively well-discussed [ 13 , 23 , 24 ]. On the other hand, although growing evidence suggests a complex interactive association between CNS disorders and cardiac dysfunction [ 19 , 20 , 21 , 22 ], it is still unclear whether NTs are involved in these mechanisms.…”