Proteomic Analysis of Prehypertensive and Hypertensive Patients: Exploring the Role of the Actin Cytoskeleton
Abstract
:1. Introduction
2. Results
2.1. General Characteristics of the Study Population
2.2. Distinct Proteomic Profile between Healthy, Prehypertensive, and Hypertensive Participants
2.3. Altered Protein Expression in the Control, Prehypertensive, and Hypertensive Groups
2.4. Sensitivity and Specificity of the Identified Proteins between the Study Groups
2.5. Alterations in Proteins Related to Actin Cytoskeleton between Prehypertension and Hypertension Groups
2.6. Validation of the Actin Cytoskeleton Related Proteins in an Independent Cohort
3. Discussion
Limitations of the Study
4. Materials and Methods
4.1. Study Participants
4.2. Samples Collection and Processing
4.3. Physical and Clinical Analysis
4.4. Analysis Multiplexed Aptamer-Based (SOMAscan) Proteomic Platform
4.5. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Controls | Prehypertension | Hypertension | p-Value | |
---|---|---|---|---|
Number of participants | 23 | 22 | 22 | |
Gender (M/F) | 11/12 | 12/10 | 12/10 | 0.99 |
Age | 45.2 ± 4.3 | 51.7 ± 5.4 | 50.2 ± 9.1 | 0.003 |
BMI | 26 ± 3.1 | 26.8 ± 2 | 26.92 ± 2.3 | 0.39 |
BMI (Males) | 27.03 ± 2.1 | 26.86 ± 2 | 26.73 ± 2.4 | 0.94 |
BMI (Females) | 24.8 ± 3.7 | 26.7 ± 2.1 | 27.2 ± 2.2 | 0.15 |
Hemoglobin g/dL | 13.3 ± 1.3 | 14.3 ± 1.6 | 14.1 ± 1.6 | 0.077 |
Red Blood Cell × 106/µL | 4.8 ± 0.6 | 5 ± 0.6 | 5 ± 0.5 | 0.46 |
White Blood Cell × 103/µL | 6.01 ± 1.3 | 6.9 ± 1.9 | 5.9 ± 1.2 | 0.072 |
Cholesterol Total mmol/L | 5.04 ± 0.6 | 4.9 ± 0.7 | 5.12 ± 0.7 | 0.54 |
LDL-Cholesterol mmol/L | 2.9 ± 0.8 | 2.8 ± 0.6 | 3.12 ± 0.64 | 0.33 |
HbA1c% | 5.4 ± 0.3 | 5.4 ± 0.4 | 5.6 ± 0.4 | 0.24 |
Systolic blood pressure | 105 ± 8.4 | 127.4 ± 5.6 | 150 ± 12.4 | <0.001 |
Diastolic blood pressure | 68.5 ± 6 | 83.2 ± 6.4 | 91.9 ± 9.8 | <0.001 |
Albumin g/L | 45.9 ± 1.3 | 46.3 ± 1.9 | 46.4 ± 2.8 | 0.67 |
ALT U/L | 26.9 ± 21 | 25.5 ± 9.7 | 27.2 ± 15.1 | 0.93 |
AST U/L | 21.2 ± 6.6 | 20.6 ± 5.8 | 23 ± 9.7 | 0.55 |
C-Reactive Protein mg/L | 5.05 ± 0.2 | 5.55 ± 2 | 5.4 ± 1.4 | 0.54 |
Hypertension treatment | ||||
Tablets | 0 | 2 | 5 | 0.043 |
DASH | 0 | 2 | 5 | 0.043 |
Hypertension|Prehypertension | |||||
---|---|---|---|---|---|
UniProt | Gene | Protein Name | Log2FC | p-Value | q-Value |
P16591 | FER | Tyrosine-protein kinase Fer | 1.12 | <0.001 | <0.001 |
Q06187 | BTK | Tyrosine-protein kinase BTK | 1.03 | <0.001 | <0.001 |
Q08752 | PPID | Peptidyl-prolyl cis-trans isomerase D | 1.01 | <0.001 | 0.02 |
P41240 | CSK | Tyrosine-protein kinase CSK | 1.00 | <0.001 | <0.001 |
P05771 | PRKCB | Protein kinase C beta type (splice variant beta-II) | 0.99 | <0.001 | 0.01 |
P15498 | VAV1 | Proto-oncogene vav | 0.98 | <0.001 | <0.001 |
Q99714 | HSD17B10 | 3-hydroxyacyl-CoA dehydrogenase type-2 | 0.96 | <0.001 | <0.001 |
P30405 | PPIF | Peptidyl-prolyl cis-trans isomerase F; mitochondrial | 0.95 | <0.001 | 0.01 |
P12931 | SRC | Proto-oncogene tyrosine-protein kinase Src | 0.94 | <0.001 | <0.001 |
P18669 | PGAM1 | Phosphoglycerate mutase 1 | 0.93 | <0.001 | 0.11 |
Q04759 | PRKCQ | Protein kinase C theta type | 0.92 | <0.001 | <0.001 |
P14618 | PKM2 | Pyruvate kinase PKM | 0.92 | <0.001 | 0.01 |
P17252 | PRKCA | Protein kinase C alpha type | 0.91 | <0.001 | 0.01 |
O76074 | PDE5A | cGMP-specific 3′;5′-cyclic phosphodiesterase | 0.90 | <0.001 | <0.001 |
P67936 | TPM4 | Tropomyosin alpha-4 chain | 0.90 | <0.001 | <0.001 |
P07948 | LYNB | Tyrosine-protein kinase Lyn; isoform B | 0.90 | <0.001 | 0.01 |
Q15796 | SMAD2 | Mothers against decapentaplegic homolog 2 | 0.89 | <0.001 | 0.01 |
P31946 | YWHAB | 14-3-3 protein family | 0.89 | <0.001 | <0.001 |
O15530 | PDPK1 | 3-phosphoinositide-dependent protein kinase 1 | 0.88 | <0.001 | 0.01 |
Q9NQU5 | PAK6 | Serine/threonine-protein kinase PAK 6 | 0.88 | <0.001 | 0.01 |
Q9NYA1 | SPHK1 | Sphingosine kinase 1 | 0.87 | <0.001 | 0.01 |
P06241 | FYN | Tyrosine-protein kinase Fyn | 0.86 | <0.001 | 0.01 |
P42680 | TEC | Tyrosine-protein kinase Tec | 0.85 | <0.001 | <0.001 |
P07948 | LYN | Tyrosine-protein kinase Lyn | 0.85 | <0.001 | 0.01 |
P42574 | CASP3 | Caspase-3 | 0.85 | <0.001 | 0.01 |
O95219 | SNX4 | Sorting nexin-4 | 0.84 | <0.001 | 0.01 |
P62993 | GRB2 | Growth factor receptor-bound protein 2 | 0.84 | <0.001 | <0.001 |
Q9Y3A5 | SBDS | Ribosome maturation protein SBDS | 0.84 | <0.001 | 0.01 |
P78344 | EIF4G2 | Eukaryotic translation initiation factor 4 gamma 2 | 0.83 | <0.001 | 0.01 |
Q13557 | CAMK2D | Calcium/calmodulin-dependent protein kinase type II subunit delta | 0.83 | <0.001 | 0.01 |
P22392 | NME2 | Nucleoside diphosphate kinase B | 0.82 | <0.001 | 0.01 |
O43488 | AKR7A2 | Aflatoxin B1 aldehyde reductase member 2 | 0.81 | <0.001 | 0.01 |
Q15056 | EIF4H | Eukaryotic translation initiation factor 4H | 0.80 | <0.001 | 0.02 |
Q8N1Q1 | CA13 | Carbonic anhydrase 13 | 0.80 | <0.001 | 0.01 |
P10809 | HSPD1 | 60 kDa heat shock protein; mitochondrial | 0.80 | <0.001 | 0.02 |
Q13554 | CAMK2B | Calcium/calmodulin-dependent protein kinase type II subunit beta | 0.79 | <0.001 | <0.001 |
O00299 | CLIC1 | Chloride intracellular channel protein 1 | 0.78 | <0.001 | <0.001 |
P25098 | ADRBK1 | beta-adrenergic receptor kinase 1 | 0.78 | <0.001 | <0.001 |
P54646 | PRKAA2/B2/G1 | AMP Kinase (alpha2beta2gamma1) | 0.78 | <0.001 | 0.02 |
Q9NP97 | DYNLRB1 | Dynein light chain roadblock-type 1 | 0.77 | <0.001 | 0.01 |
P49840 | GSK3A/B | Glycogen synthase kinase-3 alpha/beta | 0.75 | <0.001 | 0.01 |
P63000 | RAC1 | Ras-related C3 botulinum toxin substrate 1 | 0.73 | <0.001 | 0.01 |
P02775 | PPBP | Connective tissue-activating peptide III | 0.73 | <0.001 | 0.02 |
P40763 | STAT3 | Signal transducer and activator of transcription 3 | 0.72 | <0.001 | 0.01 |
P31946 | YWHAB | 14-3-3 protein beta/alpha | 0.71 | <0.001 | 0.01 |
Hypertension|Prehypertension | |||||||
---|---|---|---|---|---|---|---|
Gene | Protein Name | AUC | 95% CI | p-Value | q-Value | Sensitivity% | Specificity% |
CAMK2D | Calcium/calmodulin-dependent protein kinase type II subunit delta | 0.80 | 0.65 to 0.94 | 0.0008 | 0.0051 | 90 | 77.27 |
GSK3A/B | Glycogen synthase kinase-3 alpha/beta | 0.80 | 0.66 to 0.94 | 0.0007 | 0.0059 | 80.95 | 72.73 |
LYN | Tyrosine-protein kinase Lyn | 0.80 | 0.66 to 0.93 | 0.0007 | 0.0054 | 77.27 | 76.19 |
PPIF | Peptidyl-prolyl cis-trans isomerase F | 0.80 | 0.67 to 0.93 | 0.0007 | 0.0065 | 72.73 | 76.19 |
PPBP | Connective tissue-activating peptide III | 0.80 | 0.67 to 0.93 | 0.0007 | 0.019 | 75 | 77.27 |
LYNB | Tyrosine-protein kinase Lyn; isoform B | 0.80 | 0.67 to 0.93 | 0.0006 | 0.0054 | 72.73 | 76.19 |
GRB2 | Growth factor receptor-bound protein 2 | 0.81 | 0.68 to 0.94 | 0.0005 | 0.0044 | 80.95 | 77.27 |
NME2 | Nucleoside diphosphate kinase B | 0.81 | 0.67 to 0.94 | 0.0004 | 0.0057 | 85.71 | 72.73 |
RAC1 | Ras-related C3 botulinum toxin substrate 1 | 0.81 | 0.68 to 0.94 | 0.0004 | 0.0058 | 81.82 | 76.19 |
STAT3 | Signal transducer and activator of transcription 3 | 0.81 | 0.67 to 0.95 | 0.0006 | 0.0054 | 70 | 80 |
CSK | Tyrosine-protein kinase CSK | 0.81 | 0.68 to 0.94 | 0.0004 | 0.0043 | 81.82 | 71.43 |
ADRBK1 | beta-adrenergic receptor kinase 1 | 0.81 | 0.68 to 0.95 | 0.0004 | 0.0044 | 80.95 | 77.27 |
VAV1 | Proto-oncogene vav | 0.82 | 0.68 to 0.95 | 0.0003 | 0.0044 | 81.82 | 76.19 |
YWHAB | 14-3-3 protein beta/alpha | 0.82 | 0.68 to 0.95 | 0.0004 | 0.0061 | 90 | 77.27 |
TPM4 | Tropomyosin alpha-4 chain | 0.82 | 0.69 to 0.95 | 0.0003 | 0.0047 | 77.27 | 85.71 |
FER | Tyrosine-protein kinase Fer | 0.82 | 0.68 to 0.96 | 0.0003 | 0.0045 | 72.73 | 95 |
SRC | Proto-oncogene tyrosine-protein kinase Src | 0.83 | 0.70 to 0.96 | 0.0002 | 0.0041 | 72.73 | 80.95 |
PKM2 | Pyruvate kinase PKM | 0.83 | 0.70 to 0.96 | 0.0002 | 0.005 | 81.82 | 80 |
TEC | Tyrosine-protein kinase Tec | 0.83 | 0.70 to 0.96 | 0.0002 | 0.002 | 95.24 | 72.73 |
PDE5A | cGMP-specific 3′;5′-cyclic phosphodiesterase | 0.83 | 0.71 to 0.96 | 0.0002 | 0.0042 | 80.95 | 77.27 |
CLIC1 | Chloride intracellular channel protein 1 | 0.83 | 0.71 to 0.96 | 0.0001 | 0.00072 | 90.48 | 77.27 |
PRKCQ | Protein kinase C theta type | 0.84 | 0.71 to 0.97 | 0.0002 | 0.0025 | 80.95 | 85 |
PDPk1 | 3-phosphoinositide-dependent protein kinase 1 | 0.84 | 0.72 to 0.96 | 0.0002 | 0.005 | 72.73 | 84.21 |
BTK | Tyrosine-protein kinase BTK | 0.84 | 0.72 to 0.97 | 0.0001 | 0.0046 | 81.82 | 85 |
CAMK2B | Calcium/calmodulin-dependent protein kinase type II subunit beta | 0.85 | 0.71 to 0.98 | <0.0001 | 0.0013 | 100 | 81.82 |
SBDS | Ribosome maturation protein SBDS | 0.85 | 0.74 to 0.97 | <0.0001 | 0.0052 | 80.95 | 76.19 |
HSD17B10 | 3-hydroxyacyl-CoA dehydrogenase type-2 | 0.86 | 0.76 to 0.97 | <0.0001 | 0.0008 | 76.19 | 80 |
Gene | Protein Name | Validation Cohort | Discovery Cohort | ||
---|---|---|---|---|---|
AUC | p-Value | AUC | p-Value | ||
RAC1 | Ras-related C3 botulinum toxin sub-strate 1 | 0.83 | 0.0003 | 0.81 | 0.0004 |
VAV1 | Proto-oncogene vav | 0.79 | 0.001 | 0.82 | 0.0003 |
CAMK2B | Calcium/calmodulin-dependent protein kinase type II subunit beta | 0.78 | 0.003 | 0.85 | <0.0001 |
CAMK2D | Calcium/calmodulin-dependent protein kinase type II subunit delta | 0.75 | 0.007 | 0.80 | 0.0008 |
GSK3 | Glycogen synthase kinase-3 | 0.83 | 0.0003 | 0.80 | 0.0007 |
GRB2 | Growth factor receptor-bound protein 2 | 0.75 | 0.008 | 0.81 | 0.0005 |
LYNB | Tyrosine-protein kinase Lyn; isoform B | 0.81 | 0.001 | 0.80 | 0.0006 |
LYN | Tyrosine-protein kinase Lyn | 0.82 | 0.001 | 0.80 | 0.0007 |
CSK | Tyrosine-protein kinase CSK | 0.84 | 0.0002 | 0.81 | 0.0004 |
TPM4 | Tropomyosin alpha-4 chain | 0.81 | 0.001 | 0.82 | 0.0003 |
SRC | Proto-oncogene tyrosine-protein kinase Src | 0.79 | 0.002 | 0.83 | 0.0002 |
YWHAB | 14-3-3 protein beta/alpha | 0.82 | 0.001 | 0.82 | 0.0004 |
TEC | Tyrosine-protein kinase Tec | 0.76 | 0.005 | 0.83 | 0.0002 |
FER | Tyrosine-protein kinase Fer | 0.81 | 0.001 | 0.82 | 0.0003 |
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Al Ashmar, S.; Anlar, G.G.; Krzyslak, H.; Djouhri, L.; Kamareddine, L.; Pedersen, S.; Zeidan, A. Proteomic Analysis of Prehypertensive and Hypertensive Patients: Exploring the Role of the Actin Cytoskeleton. Int. J. Mol. Sci. 2024, 25, 4896. https://doi.org/10.3390/ijms25094896
Al Ashmar S, Anlar GG, Krzyslak H, Djouhri L, Kamareddine L, Pedersen S, Zeidan A. Proteomic Analysis of Prehypertensive and Hypertensive Patients: Exploring the Role of the Actin Cytoskeleton. International Journal of Molecular Sciences. 2024; 25(9):4896. https://doi.org/10.3390/ijms25094896
Chicago/Turabian StyleAl Ashmar, Sarah, Gulsen Guliz Anlar, Hubert Krzyslak, Laiche Djouhri, Layla Kamareddine, Shona Pedersen, and Asad Zeidan. 2024. "Proteomic Analysis of Prehypertensive and Hypertensive Patients: Exploring the Role of the Actin Cytoskeleton" International Journal of Molecular Sciences 25, no. 9: 4896. https://doi.org/10.3390/ijms25094896