3. Therapeutic application of autophagy modulators for treating
pathological cardiac hypertrophy
There are a lot of therapeutic approaches for HF, in which cardiac
pacemaker is one of the conventional treatments. However, for some
partial HF patients, cardiac pacemaker implantation is expensive and
patients’ compliance with routine physical exercise is poor [70,
71]. Drug therapy is widely available, mainly because of its lower
cost [2, 72]. However, due to a series of factors (e.g., adverse
drug reactions), there are few drugs with excellent efficiency and good
safety in treatment of pathological cardiac hypertrophy. For example,
angiotensin-converting enzyme (ACE) inhibitors often lead to side
effects in partial patients, such as coughing and kidney damage, which
significantly limits the use of ACE inhibitors [72]. A lot of
studies have shown that autophagy may be a potential target for cardiac
hypertrophy and autophagy modulators may be a promising strategy for the
treatment of cardiac hypertrophy (Table 1) [11, 53, 73].
Of note, numerous evidence suggested that modulating autophagy may
prevent or cure cardiac hypertrophy, but there were some limitations in
detecting and analyzing cardiac autophagy:
(i)
Firstly, due to variability between cardiomyocytes, animals or clinical
samples, there was a discrepancy for detecting autophagic flux, which
may not accurately represent the true connection between the heart
function and autophagy [74, 75]. (ii) Secondly, the mechanism of
autophagy-related drugs in cardiac hypertrophy requires to be further
studied, and their effects on cardiac hypertrophy may not be entirely
originated from autophagy-related pathways [24, 74]. (iii) Thirdly,
at present, there are few clinical examples using autophagy modulators
to treat pathological myocardial hypertrophy. Therefore, it is necessary
to pay close attention to the physiological indexes of patients after
drug treatment, especially the side effects of drug treatment [76].
(iv) Finally, existing autophagy modulators showed a low specificity for
diseases. Thus, how to avoid the side effects of excessively high or low
autophagic activity in patients with cardiac myocardial hypertrophy
after taking autophagic modulators remains to be further investigated.