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.