Catestatin as a Biomarker of Cardiovascular Diseases: A Clinical Perspective

Abstract

Accounting for almost one-third of the global mortality, cardiovascular diseases (CVDs) represent a major global health issue. Emerging data suggest that most of the well-established mechanistic explanations regarding the cardiovascular pathophysiology are flawed, and cannot fully explain the progression and long-term effects of these diseases. On the other hand, dysregulation of the sympathetic nervous system (SNS) has emerged as an important player in the pathophysiology of CVDs. Even though upregulated SNS activity is an essential compensatory response to various stress conditions, in the long term, it becomes a major contributor to both cardiac dysfunction and vascular damage. Despite the fact that the importance of SNS hyperactivity in the setting of CVDs has been well-appreciated, its exact quantification and clinical application in either diagnostics or therapy of CVDs is still out of reach. Nevertheless, in recent years a number of novel laboratory biomarkers implicated in the pathophysiology of SNS activation have been explored. Specifically, in this review, we aimed to discuss the role of catestatin, a potent physiological inhibitor of catecholamine spillover that offers cardioprotective effects. Limited data indicate that catestatin could also be a reliable indirect marker of SNS activity and it is likely that high CST levels reflect advanced CV disease burden. Consequently, large-scale studies are required to validate these observations in the upcoming future.

Role of Catestatin in the Cardiovascular System and Metabolic Disorders

“…Concerning the central nervous system, Cts plays an important role in cardiorespiratory control ( 14 ). Gaede et al showed that Cts antagonizes both nAChR and β-adrenergic receptors involved in cardiovascular regulation using urethane-anesthetized, vagotomized rats.…”

“…Further studies showed that Cts inhibits CA release also due to adenylate cyclase-activating polypeptide stimulation and regulates dense core vesicle quanta ( 13 ) ( Figure 1 ). Moreover, Cts has emerged as a pleiotropic peptide, which – among others – is involved in the regulation of the cardiovascular and immune system, as well as metabolic homeostasis ( 14 , 17 , 25 – 27 ).…”

“…(A) Injection of Cts into the CVLM or the central amygdala (not shown) of rats decreases sympathetic barosensitivity and attenuates peripheral chemoreflex with consequent hypotension. On the other hand, injection of Cts into the RVLM increases barosensitivity and attenuates chemosensitivity with consequent elevation of blood pressure ( 14 ). (B) Cts inhibits CA release by binding to nicotinic acetylcholine receptors that block Na + uptake ( 15 ) as well as due to PACAP stimulation ( 13 ).…”

Biomarkers of Volume Overload and Edema in Heart Failure With Reduced Ejection Fraction

“…Nevertheless, these mechanisms have deleterious effects on cardiac structure and performance, leading not only to symptomatic HF, but also to HF decompensations. In addition, higher levels of plasma circulating NA seen from Stage B in HF, were strongly linked to a worsening of systolic dysfunction and a progression of interstitial fluid accumulation, marking the onset of edema formation at biochemical/molecular level (26)(27)(28)(29)(30).…”

“…Specifically, CgA demonstrated to be a powerful predictive marker of mortality and morbidity in HF subjects (28). It inhibits cardiac remodeling, reduce arterial blood pressure and decrease endothelial and vascular inflammation (24,28,29). The last two mentioned effects may suggest its involvement in body fluid homeostasis, thus an increased circulating plasma level of CgA observed in HF patients, would translate as a compensatory mechanism meant to limit acute/chronic fluid overload.…”