Review Article

Effects of Hypertension and Exercise on Cardiac Proteome Remodelling

Table 1

Cardiac proteome modulated by pathologic cardiac hypertrophy.

Experimental modelExperimental methodMain altered proteomeReference

SHR and WKY 2D-DIGEComparison between different SHR age and animal models:
(i) 33 mitochondrial proteins with altered expression between SHR groups;
(ii) Hadha and NDUFA10 with differential patterns in SHR versus WKY.
[45]

SHRPhosphoaffinity chromatography; 2-DE;
Pro-Q staining;
MALDI TOF
Protein phosphorylation in cardiac hypertrophy linked with hypertension:
(i) 3-ketoacyl-CoA thiolase;
(ii) α-enolase hyperphosphorilation (reduced enzymatic activity);
(iii) SR-Ca2+-ATPase and phospholamban.
[40, 47]

Human heart tissueTop-down MS-based quantitative proteomicsPhosphorylation of cTnl in Serine 22/23 as candidate biomarker of CHF.[82]

SHR versus RHR and WKY2D-DIGE/MALDI TOFComparison between two distinct models of heart hypertrophy:
(i) 29 protein spots with differential expression among the three groups (18 proteins identified);
(ii) GSTM2 and SCAD in RHR versus WKY;
(iii) Distinct profile of GSTM2 and SCAD between SHR and RHR.
[49]

WKY2-DE/MALDI TOF;
Pharmacologic treatment
Effect of pharmacologic treatment over LVH regression:
(i) 36 proteins altered in hypertensive heart;
(ii) SCAD, NADH, enolase 1 , and aldehyde dehydrogenase;
(iii) ETF- , superoxide dismutase, and thiol-specific antioxidant.
[50]

Animal model lacking Kir6.2 ATP-sensitive K(+) (K(ATP)) channels2-DE; LC-MS/MS;
Orbitrap MS
Deficiency in myocardial KATP channels and hypertension pathophysiology:
(i) 170 proteins with differential expression in response to KATP channel dysfunction;
(ii) LDH, SCAD, pyruvate kinase, TPI, and CK.
[5153]

Animal model and humanTranscriptomeProteinases and the pathophysiology of hypertension:
(i) Induction of cardiac hypertrophy by Ang II;
(ii) Attenuation of cardiac hypertrophy by Ang II and RAS inhibition.
[41, 6266]

dTGR and Sprague-Dawley ratsLC-MS/MSCaloric restriction in dTGR over mitochondrial proteins:
(i) 7 differential proteins after caloric restriction in Dtgr;
(ii) 6 proteins unique to dTGR compared to caloric restricted dTGR and SD rats;
(iii) 6 proteins (cytoskeletal and enzyme modulators) and 
oxidoreductase.
[69]

dTGRGas-chromatography TOFCardiac hypertrophy induced by Ang II:
Modulation of >100 cardiac metabolites.
[70]

Aortic constriction in rodent modelLabel-free LC-MS/MSPressure overload cardiac hypertrophy:
(i) mitochondrial fatty acid oxidation proteins;
(ii) pyruvate dehydrogenase subunits and TCA proteins.
[71]

Animal model and cell culture2-DE; LC ESI-MS/MSCardiac hypertrophy induced by ET-1 and leukemic inhibitory factor exposure:
(i) Differential proteome between ET-1 (concentric) and eccentric induced hypertrophy;
(ii) B-crystalline in nontreated cells;
(iii) ANP upregulated in both cardiac hypertrophy models;
(iv) desmin protein species.
[43, 79]

Animal model and cell culture2-DE MS/MSCardiac hypertrophy induced by ISO:
(i) 7 differential expressions in heart induced with ISO;
(ii) MLC 2 and 3, desmin, prohibitin, FABP-H, and ATP-synthase 5 ;
(iii) HSP60, 70, and D1.
[80, 81]

ANP: atrial natriuretic polypeptide; CHF: chronic heart failure; CK: creatine kinase; cTnl: cardiac troponin; dTGR: double transgenic rats harbouring human renin and angiotensin genes; ET-1: endothelin-1; ETF- : electron transfer flavoproteins- ; FABP-H: heart fatty acid binding protein; GSTM2: glutathione-S-transferase; Hadha: mitochondrial trifunctional enzyme alpha subunit; HSP: heat shock proteins 60, 70, and D1; ISO: isoproterenol; LDH: lactate dehydrogenase; LVH: left ventricle hypertrophy; MLC 2 and 3: myosin light chain 2 and 3; NDUFA10: NADH dehydrogenase 1 alpha subcomplex 10; RHR: animal model of secondary hypertension performed by clipping renal arteries; SCAD: Short-chain acyl-CoA dehydrogenase; SHR: spontaneously hypertensive rat; TCA: tricarboxylic cycle; TPI: triosephosphate isomerase; WKY: Wistar-Kyoto; -MHC: -myosin heavy chain.