Table 4 |.
lncRNAs that could function as biomarkers for cardiac hypertrophy and cardiac disease
| lncRNAs | Models | Observed change / study findings | Study population parameters | Ref. |
|---|---|---|---|---|
| aHIF, ANRIL, KCNQ1OT1, MALAT1, MIAT | Human | Whole-blood levels of aHIF, KCNQ1OT1 and MALAT1 were higher in patients with MI, whereas the level of ANRIL was lower; the level of MIAT was similar in both groups | Patients with STEMI: n = 274, male/female = 199/75, median age 61 years, range 35–89 years; patients with NSTEMI: n = 140, male/female = 102/38, median age 62 years, range 30–89 years; controls: n = 86, male/female = 70/16, median age 61 years, range 25–82 years | 180 |
| Ahit | Human | Upregulated in serum samples from patients with hypertensive heart disease (compared with individuals with non-hypertrophic hearts) | Patients with cardiac hypertrophy: male/female = 6/5; controls: male/female = 8/7 | 163 |
| BACE1, BACE1-as | Human and mouse | Levels of both transcripts increased in tissue biopsied from left ventricle of patients with HF; transcript levels also increased in a mouse model of ischaemic HF | Patients with HF: n = 18, male/female = 17/1; aged 65.0 ± 0.6 years; controls: n = 17, male/female = 10/6 (noted discrepancy in numbers from report); aged 58.3 ± 3.4 years | 181 |
| Carmen, Fendrr, Mhrt | Human | Left ventricular mass index showed a negative correlation with levels of Mhrt and Fendrr and a positive correlation with levels of Carmen; analysis performed using peripheral blood mononuclear cells from patients with essential hypertension associated with left ventricular hypertrophy | Patients with hypertension: n = 80, male/female = 32/48, aged 67 ± 8 years; controls: n = 25, male/female = 8/17, aged 64 ± 5 years | 182 |
| H19 | Human | Single-nucleotide polymorphisms identified that affect the secondary structure of H19 | Patients with DCM: n = 96, male/female = 70/26, mean age 53 years, range 22–80 years; controls: n = 259, male/female = 129/130, from the 1000 Genomes Project); variants confirmed with cohort of 1,084 patients with DCM and 751 disease-free controls (overall mean age 43 (range 0–83) years, 31% female) | 183 |
| Human, mouse and rat | Dynamically expressed in pathological hearts (changes observed in patient plasma samples, as well as in TAC mouse model of cardiac hypertrophy and rat model of right ventricular failure (monocrotaline treated and pulmonary artery banded)) | Aortic stenosis: n = 24, male/female = 16/8, aged 70 ± 17 years; HCM: n = 12, male/female = 6/6; aged 17 ± 20 years; control hearts: n = 24, male/female = 14/10, aged 39 ± 13 years. Failing hearts: n = 12, male/female = 7/5, aged 72 ± 4 years, fetal hearts: n = 4, aged 12–14 weeks; control (non-failing) hearts: n = 4, male/female = 2/2, aged 48 ± 4 years. LVAD hearts: n = 12, male/female = 9/3, aged 54 ± 6 years; LVAD control hearts: n = 9, male/female = 1/8, aged 40 ± 13 years. 61,67Patients with IPAH: n =52, male/female = 21/31, aged 61 ± 16 years; patients with CTD-IPAH: n = 21, male/female = 5/16, aged 69 ± 8 years; controls: n = 57, male/female = 40/17, aged 46 ± 19 years61,67 | 61,67 | |
| Human | H19 variants associated with elevated risk of developing HCM; genotyped two H19 SNPs in 405 patients with HCM and 550 controls; sequence determined in 100 patients; the incidence of the H19 rs2107425 CC genotype (C homozygous) was higher in patients without sarcomere mutations | Patients with sarcomere-negative HCM: n = 225, male/female = 140/85, aged 56 ± 14 years; patients with sarcomere-positive HCM: n = 180, male/female = 117/63, aged 46 ± 12 years; controls: n = 550, aged 60–85 years | 184 | |
| H19 and LIPCAR | Human | Increased plasma levels associated with increased risk of coronary artery disease in a Chinese population | Patients with coronary artery disease: n = 300, male/female = 188/112, aged 64 ± 11 years; controls: n = 180, male/female = 108/72, aged 63 ± 10 years | 185 |
| H19, HOTAIR, RMRP | Human and mouse | Levels increased in tissue biopsied from left ventricle of patients with ischaemic DCM; also increased in TAC mouse model of cardiac hypertrophy | Patients with ischaemic DCM or HF: n = 18, male/female = 17/1, aged 65 ± 1 years; controls: n = 16, male/female = 10/6, aged 58 ± 3 years | 186 |
| Heat2 | Human | Levels elevated in the blood of patients with HF; enriched in circulating immune cells | Next-generation sequencing cohort (cohort 1): patients with HF: n = 4, male/female = 4/0, aged 62 ± 14.5 years; controls: n = 4, male/female = 4/0, aged 29 ± 2.8 years. First validation cohort (cohort 2): patients with HF: n = 16, male/female = 3/13, aged 65 ± 11.1 years; controls: n = 8, male/female = 2/6, aged 64 ± 5.2 years. Second validation cohort (cohort 3): patients with HF: n = 69, male/female = 58/11, aged 65 ± 10.5 years; controls: n = 38, male/female = 27/11, aged 63.5 ± 12.1 years | 187 |
| LIPCAR188,189 | Human | Plasma levels increased in patients with HF and higher NYHA class | LIPCAR subcohort: patients with HF: n = 967, male/female = 775/192, aged 70 ± 10.8 years | 190 |
| Human | Increased plasma levels in patients with HF after acute MI | Patients with HF after acute MI: n = 59, male/female = 33/26, aged 64 ± 7.2 years; patients without HF after acute MI: n = 68, male/female = 39/29, aged 63 ± 10.5 years | 191 | |
| Human | Plasma levels elevated in patients with HF with reduced ejection fraction and associated with left ventricular remodelling and poor outcomes | Patients with CKD: n = 100, male/female = 41/59, aged 77 ± 8.7 years; patients without CKD: n = 134, male/female = 117/117, aged 72 ± 8.9 years | 192 | |
| Human | Initially downregulated after MI but upregulated during later stages (plasma RNA isolated from three independent cohorts (788 patients) who developed HF with abnormal cardiac remodelling) | Cohort with left ventricular remodelling: patients with acute MI: n = 246, male/female = 200/46, aged 57 ± 14 years. First cohort with HF: patients with ischaemic HF: n = 164, male/female = 136/28; aged 56 ± 11 years; patients with non-ischaemic HF: n = 180, male/female = 139/41, aged 53 ± 11 years. Second cohort with HF: patients with HF and subsequent cardiovascular death: n = 99, male/female = 91/8, aged 59 ± 11 years; patients with HF and no subsequent cardiovascular death: n = 99, male/female = 91/8, aged 59 ± 11 years | 188 | |
| lncCytB | Human and mouse (TAC model) | Plasma levels decreased in patients with HF; cytosolic lncRNA | Patients with HF: n = 12, male/female = 6/6, aged 60 ± 2.8 years; controls: n = 11, male/female = 5/6, aged 54 ± 2.4 years | 168 |
| lncExACT1 | Human | Increased plasma levels in patients with HF | Patients with HF with reduced ejection fraction: n = 18; patients with HF with preserved ejection fraction: n = 16; controls or patients with supraventricular tachycardia but no HF: n = 8 | 158 |
| LncHrt | Human | Levels decreased in the hearts of patients with DCM | Patients with DCM: n = 6, aged 49–68 years; controls: n = 2, aged 15–30 years | 193 |
| lncRNA ENST00000507296 and ENST00000532365 | Human | Plasma levels of lncRNAs ENST00000507296 and ENST00000532365 correlated with cardiac function in patients with DCM | Screening cohort: patients with DCM: n = 10, male/female = 9/1, aged 63–82 years; controls: n = 10, male/female = 10/0, aged 33–56 years. Validation cohort: patients with DCM: n = 64, male/female = 42/22, aged 56 ± 14.6 years; controls: n = 64, male/female = 36/28, aged 56 ± 10.7 years. Replication cohort: patients with DCM: n = 198, male/female = 144/54, aged 55 ± 0.9 years; controls: n = 198, male/female = 133/65, aged 54 ± 0.7 years. Follow-up cohort: patients with DCM (with exclusion of patients with other severe systemic diseases (such as renal failure or hepatic diseases) and malignant tumours or congenital heart diseases or clinically significant valvular diseases): n = 552, male/female = 392/160, aged 55 ± 13 years | 194 |
| Mhrt | Human | Plasma levels of Mhrt were downregulated in patients with chronic HF (compared with healthy controls); potential use of circulating MHRT levels as a diagnostic and prognostic marker for chronic HF | Patients with chronic HF: n = 88, male/female = 50/38, aged 55 ± 6.6 years; controls: n = 65, male/female = 40/25, aged 54 ± 5.9 years | 195 |
| Mhrt, NRON | Human | Plasma levels of both lncRNAs higher in patients with HF than in controls (analysis conducted using real-time RT-PCR) | Patients with HF: n = 72, male/female = 47/25, aged 59 ± 11.2 years; controls: n = 60, male/female = 37/23, aged 60 ± 12 years | 196 |
| NEAT1 | Human | Increased serum levels of NEAT1 associated with decreased microRNA-129–5p expression in patients with chronic HF | Patients with chronic HF: n = 70, male/female = 37/33, aged 67 ± 1.6 years; controls: n = 62, male/female = 34/28, aged 67 ± 1.7 years | 197 |
| NRF | Human | Potential marker to determine the risk of HF after acute MI | Patients with HF after acute MI: n = 76; patients without HF after acute MI: n = 58 | 198 |
CKD, chronic kidney disease; CTD, connective tissue disease-associated; DCM, dilated cardiomyopathy; HF, heart failure; HCM, hypertrophic cardiomyopathy; IPAH, idiopathic pulmonary arterial hypertension; lncRNA, long non-coding RNA; LVAD, left ventricular assist device; MI, myocardial infarction; NSTEMI, non-ST-segment elevation myocardial infarction; TAC, transverse aortic constriction; RT-PCR, reverse transcription polymerase chain reaction; STEMI, ST-segment elevation myocardial infarction;.