**5.2 Cardiac telocytes in cardiovascular diseases**

Isolated atrial amyloidosis (IAA) is frequently found in long-standing atrial fibrillation patients [113]. By electron microscopy, telopodes are found surrounding the amyloid deposits, which limit their spreading into the interstitium [113]. This indicates that TCs might participate in amyloidogenesis by gathering masses of amyloid fibrils.

Systemic sclerosis represents a complex connective tissue disease featured with fibrosis of the skin and various internal organs [54]. TCs, as defined by CD34 positivity/CD31-negativity, were checked in the fibrotic areas of systemic sclerosis myocardium and were found to be almost undetectable [54]. However, in the control myocardium, numerous TCs were found located in the interstitium surrounding cardiomyocytes [54]. This indicates that loss of cardiac TCs contributes to myocardial fibrosis caused by systemic sclerosis.

The imbalance between cardiac TCs apoptotic death and cardiac TCs proliferation is responsible for the depletion of cardiac TCs in cardiac diseases leading to heart failure [52]. In human heart failure patients' myocardium, the number of cardiac TCs and telopodes decreases over twofold. Additionally, the apoptotic cardiac TCs increases threefold in the diseased heart while the percentage of proliferating cardiac TCs remains unchanged, suggesting that the decreased cardiac TCs population in heart failure is mainly due to increased apoptosis [52]. Interestingly, the number of cardiac TCs and telopodes has been found to depend on the composition of the extracellular matrix which is correlated negatively with mature fibrillar collagens and positively with degraded collagens [52].

The changes of cardiac TCs have been determined in an acute myocardial infarction rat model induced by isoproterenol (ISO) [114]. It was found that CD117/CD34 positive cardiac TCs were undetectable with immunohistochemical staining 1 day after ISO treatment. Interestingly, treatment with grape seed extract (GSE) could significantly increase cardiac TCs numbers and enhance angiogenesis in myocardia but not in other tissues; in fact, it was found suppressing angiogenesis in tumor tissues instead [114]. Thus, GSE was regarded to promote angiogenesis by modulating cardiac TCs, which subsequently stimulated endothelial cells [114].

Also, in a rat myocardial infarction model induced by coronary occlusion, cardiac TCs were reported undetectable in the infarction zone from 4 days to 4 weeks [115]. Simultaneous transplantation of cardiac TCs could significantly decrease infarct size and improve heart function 2 weeks after myocardial infarction [115]. Moreover, the protective effects of intramyocardial transplantation of cardiac TCs were also observed 14 weeks after myocardial infarction as evidenced by improved heart function, decreased infarct size, increased angiogenesis, and decreased myocardial fibrosis [116].

Currently, no single specific immunophenotype for cardiac TCs has been identified [101]. For in-depth studies of cardiac TCs, it is highly needed to identify a specific immunostaining marker for them. Most isolated cardiac TCs are either not pure enough (as cardiac fibroblasts grow much faster than cardiac TCs) or only containing subtypes of cardiac TCs. It would be beneficial to investigate the therapeutic effects of cardiac TCs or cardiac TCs-derived exosomes. Moreover, the immunoregulatory effects of cardiac TCs should be thoroughly investigated. Finally, other organs or tissue-specific TCs are worthy to be studied.
