Abstract
Neurocardiovascular diseases (NCVD) are the leading cause of death in the developed world and will remain so till 2020. In these diseases the pathologically changed nervous control of cardiovascular system has the central role. The actual NCV syndromes are neurogenic hypertension, representing the sympathetically mediated disorder, and vasovagal syncope, which is the vagally mediated disorders. Vasovagal syncope, the disease far from its etiological treatment, could benefit from recruiting and application of antimuscarinic drugs used in other parasympathetic disorders. The informational spectrum method (ISM), a method widely applied for the characterization of protein-protein interactions in the field of immunology, endocrinology and anti HIV drug discovery, was applied for the first time in the analysis of neurogenic hypertension and vasovagal syncope therapeutic targets. In silico analysis revealed the potential involvement of apelin in neurogenic hypertension. Applying the EIIP/ISM bioinformatics concept in investigation of drugs for treatment of vasovagal syncope suggests that 78% of tested antimuscarinic drugs could have anti vasovagal syncope effect. The presented results confirm that ISM is a promissing method for investigation of molecular mechanisms underlying pathophysiological proceses of NCV syndromes and discovery of therapeutics targets for their treatment.
Highlights
Neurocardiovascular diseases (NCVD) are the syndromes where autonomic nervous system (Zoccoli et al, 2001; Bojic, 2003) dysfunction plays a dominant etiological role (Goldstain, 2001; Bojic et al, 2012a,b)
The primary structure of proteins encodes the information represented by the informational spectrum (IS) frequencies that correspond to the protein biological function
By performing cross-spectral analysis (CS) of MAS receptor and Angiotensin 1-7 (Ang 1-7) we have identified that these two molecules share common information corresponding to the Informational spectrum (IS) frequency F(0.057) (Figure 2D)
Summary
NCVD are the syndromes where autonomic nervous system (Zoccoli et al, 2001; Bojic, 2003) dysfunction plays a dominant etiological role (Goldstain, 2001; Bojic et al, 2012a,b). NCV disorders can be classified as sympathetically mediated disorders (i.e., neurogenic hypertension, NH) vs vagally mediated disorders (i.e., vasovagal syncope, VVS), though in many disorders both systems are dysfunctional (Goldstain, 2001). NH is characterized by an increased level of sympathetic nervous activity (SNA) (Fisher and Paton, 2011). SNA is in reciprocal interaction with the number of important systems for the pathophysiological profile of NH, like inflammation, angiotension II system and vascular dysfunction. Due to its potential causal role in the genesis of NH, an emphasis was put on the role of oxidative stress in brain stem structures.
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