Table 1.
Characteristics and key findings of included studies
| Drug class | Sample size, median (range) | Exposure to treatment, mean (SD) | Effect on ACE2 expression, levels or activity (number of studies)* | Model tested (number of studies)* | Site of ACE2 receptor measurement (number of studies)* | Condition of subjects (number of studies)* |
| ACE inhibitors27–36 | 32 (7–375) | 4 weeks (3) | Increase (n=17) Decrease (n=1) No effect (n=4) |
Rats, in vivo (n=16) Humans, in vivo (n=2) Other (n=4) |
Cardiac (n=14) Hepatic (n=2) Renal (n=2) Not stated (n=2) Other (n=3) |
Heart disease/heart failure (n=7) Hypertension (n=3) Diabetes (n=3) Healthy (n=2) Other (n=1) Not stated (n=6) |
| Aldosterone antagonists37–39 | 63 (28–75) | 4 weeks (4) | Increase (n=3) Decrease (n=0) No effect (n=0) |
Rats, in vivo (n=3) | Renal (n=3) | Diabetes (n=1) Renal disease (n=1) Hepatic dysfunction (n=1) |
| Angiotensin receptor blockers28 30 35 36 40–89 | 36 (6–180) | 6 weeks (6) | Increase (n=43) Decrease (n=7) No effect (n=3) Unclear/mixed findings (n=2) |
Rats, in vivo (n=34) Mice, in vivo (n=11) Humans, in vivo (n=4) Other (n=6) |
Cardiac (n=27) Hepatic (n=2) Renal (n=12) Lung (n=2) Not stated (n=1) Other (n=7) |
Hypertension (n=13) Heart disease/heart failure (n=10) Diabetes (n=5) Healthy (n=6) Not stated (n=13) Other (n=5) |
| Beta blockers63 90 | 52 (44–62) | 4 weeks (2) | Increase (n=0) Decrease (n=0) No effect (n=2) |
Rats, in vivo (n=1) Rats, in vitro (n=1) |
Cardiac (n=2) | Hypertension (n=2) |
| Calcium channel blockers51 91 92 | 117 (N/A) | 3 weeks (1) | Increase (n=2) Decrease (n=1) No effect (n=0) |
Rats, in vivo (n=2) Human, in vitro (n=1 |
Hepatic (n=1) Cardiac (n=1) Cerebral (n=1) |
Healthy (n=2) Hypertension (n=1) |
| Centrally acting vasodilators86 | 6 (N/A) | 8 weeks (N/A) | Increase (n=0) Decrease (n=0) No effect (n=1) |
Mice, in vitro (n=1) | Cardiac (n=1) | Other (n=1) |
| DPP4 inhibitor93 | 24 (N/A) | 4 weeks (N/A) | Increase (n=1) Decrease (n=0) No effect (n=0) |
Rats, in vivo (n=1) | Cardiac (n=1) | Healthy (n=1) |
| GABA analogues94 | 8 (N/A) | 3 weeks (N/A) | Increase (n=0) Decrease (n=1) No effect (n=0) |
Rats, in vivo (n=1) | Cerebral (n=1) | Heathy (n=1) |
| GLP-1 agonists93 95 | 38 (24–54) | 3 weeks (1) | Increase (n=2) Decrease (n=0) No effect (n=0) |
Rats, in vivo (n=2) | Cardiac (n=1) Lung (n=1) |
Diabetic (n=1) Healthy (n=1) |
| Insulin96–103 | 57 (8–84) | 6 weeks (6) | Increase (n=6) Decrease (n=1) No effect (n=1) |
Mice, in vivo (n=4) Mice, in vitro (n=1) Rats, in vivo (n=2) Rats, in vitro (n=1) |
Renal (n=5) Cardiac (n=2) |
Diabetes (n=7) Healthy (n=1) |
| Ivabradine104 | 24 (N/A) | 12 weeks (N/A) | Increase (n=1) Decrease (n=0) No effect (n=0) |
Canine, in vivo (n=1) | Cardiac (n=1) | Heart failure (n=1) |
| NSAIDs105 106 | 18 (N/A) | 8 weeks (0) | Increase (n=2) Decrease (n=0) No effect (n=0) |
Rats, in vivo (n=2) | Cardiac (n=2) | Diabetic (n=2) |
| Oestrogens45 107–111 | 27 (17–75) | 3 weeks (3) | Increase (n=3) Decrease (n=1) No effect (n=1) |
Human, in vitro (n=2) Human, in vivo (n=1) Rats, in vivo (n=2) Mice, in vivo (n=1) |
Cardiac (n=2) Ovarian (n=1) Cerebral (n=1) Not stated (n=2) |
Heart disease (n=1) Hypertension (n=1) Hypertension+ovariectomy (n=1) Healthy (n=1) Not stated (n=1) Alzheimers (n=1) |
| PDE-5 inhibitors112 | 32 | 30 min (N/A) | Increase (n=0) Decrease (n=0) No effect (n=1) |
Rats, in vitro (n=1) | Cardiac (n=1) | Healthy (n=1) |
| SGLT2 inhibitors113 | Not stated | 15 weeks (N/A) | Increase (n=0) Decrease (n=0) No effect (n=1) |
Mice, in vitro (n=1) | Renal (n=1) | Diabetic (n=1) |
| Statins92 103 114–116 | 62 (36–87) | 5 weeks (3) | Increase (n=3) Decrease (n=1) No effect (n=1) |
Rats, in vivo (n=4) Rats, in vitro (n=1) |
Cardiac (n=4) Renal (n=1) |
Diabetes (n=2) Hypertension (n=1) Unclear (n=1) Unclear (n=1) |
| Thiazide and thiazide-like diuretics117 | 48 (N/A) | 1 week (N/A) | Increase (n=1) Decrease (n=1) No effect (n=0) |
Rats, in vivo (n=1) | Cardiac (n=1) | Hypertension (n=1) Healthy (n=1) |
| Thiazolidinedione105 118–123 | 21 (8–60) | 6 weeks (8) | Increase (n=5) Decrease (n=1) No effect (n=1) |
Rats, in vivo (n=4) Rats, in vitro (n=1) Human, in vitro (n=1) Mice, in vivo (n=1) |
Renal (n=3) Cardiac (n=2) Hepatic (n=1) Cerebral (n=1) |
Hypertension (n=1) Heart disease/heart failure (n=1) Diabetes (n=1) Healthy (n=1) Renal disease (n=1) Not stated (n=2) |
| Vitamin D123–125 | 47 (33–60) | 6 weeks (6) | Increase (n=2) Decrease (n=0) No effect (n=1) |
Rats, in vivo (n=3) | Cardiac (n=1) Renal (n=1) Not stated (n=0) |
Hypertension (n=1) Renal disease (n=1) Not stated (n=1) |
| Vitamin D analogues126 127 | 28 (25–30) | 8 weeks (11) | Increase (n=1) Decrease (n=0) No effect (n=1) |
Rats, in vivo (n=1) Rats, in vitro (n=1) |
Renal (n=1) Lung (n=1) |
Diabetes (n=5) Lung injury (n=1) |
| Zinc(128) | Not stated | Not stated | Increase (n=0) Decrease (n=1) No effect (n=0) |
Rats, in vitro (n=1) | Renal (n=1) Lung (n=1) |
Not stated (n=1) |
*Studies reporting on multiple sites or in multiple models have been listed separately and appear more than once in the table.
GABA, gamma-Aminobutyric acid; GLP-1, glucagon-like peptide 1; PDE-5 inhibitor, phosphodiesterase type 5 inhibitor.