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Published on: August 28, 2016
Proteostasis Response to Protein Misfolding in Controlled Hypertension
Manuel Teixeira1, Dário Trindade1, Marisol Gouveia1
1Department of Medical Sciences, Institute of Biomedicine-iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal.
Insights
Hypertension engages protein homeostasis (proteostasis) mechanisms to maintain proteome stability. Even with controlled blood pressure, associations between Endothelin 1 and protein aggregation indicate active coping strategies in hypertensive individuals.
Area of Science:
- Cardiovascular Disease Research
- Molecular Biology
- Proteostasis Mechanisms
Background:
- Hypertension is a primary risk factor for cardiovascular diseases, necessitating research into its underlying mechanisms.
- Recent studies link hypertension to disruptions in protein homeostasis (proteostasis), impacting cellular health.
- Understanding proteostasis in hypertension is crucial for developing targeted interventions.
Purpose of the Study:
- To investigate and characterize proteostasis in plasma samples from individuals with controlled hypertension.
- To compare proteostasis markers between hypertensive and normotensive individuals.
- To explore associations between hypertension-related factors and protein aggregation.
Main Methods:
- Analysis of plasma samples from 40 individuals (20 with controlled hypertension, 20 matched controls).
- Quantification of protein aggregates using fluorescent probes (Proteostat, Thioflavin T) and slot blot immunoassays.
- Assessment of proteostasis-related proteins (Ubiquitin, Clusterin) and Fourier-transform infrared spectroscopy (FTIR).
Main Results:
- No significant differences in absolute levels of protein aggregates or proteostasis proteins between groups.
- Significant positive associations found between Endothelin 1 and protein aggregation/proteostasis biomarkers in the hypertension group.
- Correlations observed between quality control proteins and protein aggregates specifically in hypertensive individuals.
Conclusions:
- Proteostasis mechanisms are actively involved in hypertension as a compensatory response.
- These mechanisms attempt to mitigate pathological effects on proteome stability, even under medication.
- Findings highlight the dynamic role of proteostasis in managing hypertension's cellular impact.
Abstract:
Hypertension is the most determinant risk factor for cardiovascular diseases. Early intervention and future therapies targeting hypertension mechanisms may improve the quality of life and clinical outcomes. Hypertension has a complex multifactorial aetiology and was recently associated with protein homeostasis (proteostasis). This work aimed to characterize proteostasis in easy-to-access plasma samples from 40 individuals, 20 with controlled hypertension and 20 age- and gender-matched normotensive individuals. Proteostasis was evaluated by quantifying the levels of protein aggregates through different techniques, including fluorescent probes, slot blot immunoassays and Fourier-transform infrared spectroscopy (FTIR). No significant between-group differences were observed in the absolute levels of various protein aggregates (Proteostat or Thioflavin T-stained aggregates; prefibrillar oligomers and fibrils) or total levels of proteostasis-related proteins (Ubiquitin and Clusterin). However, significant positive associations between Endothelin 1 and protein aggregation or proteostasis biomarkers (such as fibrils and ubiquitin) were only observed in the hypertension group. The same is true for the association between the proteins involved in quality control and protein aggregates. These results suggest that proteostasis mechanisms are actively engaged in hypertension as a coping mechanism to counteract its pathological effects in proteome stability, even when individuals are chronically medicated and presenting controlled blood pressure levels.
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