In summary, animal studies have shown that the processes leading to cardiac myocyte hypertrophy, interstitial fibrillar collagen degradation, mural realignment, and ultimately to dilated cardiomyopathy are induced and/or regulated, at least in part, by TNF-α.
Thus, although we found no association between CCN2 and the presence of CHD based on current criteria, our findings suggest that plasma levels of CCN2 could potentially be a marker of early cardiac fibrosis in patients with NETs reflecting both mural and valvular pathology.
Consistent with the function of murine Tie-2 in vessel and cardiac development, VMCM patients have a relative lack of mural cells in affected regions of the endothelium and some have ventricular septal defects (VSDs) (Vikkula et al., 1996; Wouters et al., 2010).
Finally, cardiac aging results in decreased mechanical and contractile efficiency, stiffening of myocardial cells, mural connective tissue and valves, decreased number of myocytes, increased myocyte size, increased rate of myocyte apoptosis, and blunted-adrenoceptor-mediated contractile and inotropic response [ 19].
Mural endocarditis is inflammation and disruption of the nonvalvular endocardial surface of the cardiac chambers.
Mural, nonocclusive, white thrombi, consisting predominantly of aggregated platelets, are the cause of cardiac ischemia in most patients (>90%) with UA. 1, 2 The pathophysiologic characteristics of non-Q wave MI are similar to those of UA, but this syndrome is accompanied by more severe ischemia and evidence of myocardial necrosis.
Detailed molecular analyses revealed the diversity of the cardiac cellulome and facilitated the development of techniques to isolate understudied cardiac cell populations, such as mural cells and glia.
Although we do not have mechanistic data, it is tempting to hypothesize that circulating serotonin may induce CCN2 expression in cardiac fibroblasts directly as well as via induction of TGF-β leading to increased collagen deposition and fibrosis in both mural and valvular endocardium.
Nonetheless, based on the potent fibrogenic properties of CCN2 as well as its relationship to cardiac fibrosis, we suggest that CCN2 is not only a marker but may also be a mediator in the development of mural and valvular pathology in patients with NETs.
