The intracellular renin–angiotensin system: implications in cardiovascular remodeling

@article{Kumar2008TheIR,
  title={The intracellular renin–angiotensin system: implications in cardiovascular remodeling},
  author={Rajesh Kumar and Vivek P. Singh and Kenneth M. Baker},
  journal={Current Opinion in Nephrology and Hypertension},
  year={2008},
  volume={17},
  pages={168–173}
}
Purpose of reviewThe renin–angiotensin system, traditionally viewed as a circulatory system, has significantly expanded in the last two decades to include independently regulated local systems in several tissues, newly identified active products of angiotensin II, and new receptors and functions of renin–angiotensin system components. In spite of our increased understanding of the renin–angiotensin system, a role of angiotensin II in cardiac hypertrophy, through direct effects on cardiovascular… 

Diversity of pathways for intracellular angiotensin II synthesis

TLDR
There is significant diversity in the mechanism of intracellular synthesis of Ang II in various cell types and pathological conditions, and observations suggest that a therapeutic intervention to block the RAS should take into consideration the nature of the disorder and the cell type involved.

Networking between systemic angiotensin II and cardiac mineralocorticoid receptors.

TLDR
The paradigm appears to be even more complex with the recent observations that not only does Ang II/AT1R mediate effects in part through transactivation of receptor tyrosine kinases, such as the epidermal growth factor receptor (EGFR) in a cell-specific manner, but that Ang II may induce some of its actions through aldosterone and its mineralocorticoid receptor (MR).

The intracellular renin-angiotensin system in the heart

TLDR
Identification of a functional intracellular RAS may address several unanswered questions regarding a direct role of angiotensin (Ang) II in cardiac remodeling and incomplete efficacy of ang Elliotensin-converting enzyme inhibitors and angiotENSin receptor blockers or superiority of a renin inhibitor in cardiovascular disorders.

Evidence for a functional intracellular angiotensin system in the proximal tubule of the kidney.

TLDR
A comprehensive review of the intracellular actions of ANG II, either administered directly into the cells or expressed as an intrace cellularly functional fusion protein, and its effects throughout a variety of target tissues susceptible to the impacts of an overactive Ang II, with a particular focus on the proximal tubules of the kidney.

Novel Aspects of the Cardiac Renin–Angiotensin System

TLDR
Ang II-independent RAS actions suggest that efficacy of angiotensin receptor blockers (ARBs) and ACE inhibitors would have limitations in the treatment of diabetic patients, and it is confirmed that the AT1-independent effects of iAng II are likely mediated by novel interactions between Ang II and intracellular proteins.

Activation of the intracellular renin-angiotensin system in cardiac fibroblasts by high glucose: role in extracellular matrix production.

TLDR
Cardiac fibroblasts contain a functional intracellular RAS that participates in extracellular matrix formation in high glucose conditions, an observation that may be helpful in developing an appropriate therapeutic strategy in diabetic conditions.

The intracrine renin-angiotensin system.

TLDR
The RAS seems relevant at the cellular level, wherein individual cells have a complete system, termed the intracellular RAS, and from cells to tissues to the entire organism, the RAS exhibits continuity while maintaining independent control at different levels.
...

References

SHOWING 1-10 OF 68 REFERENCES

Cardiac and Vascular Renin-Angiotensin Systems

TLDR
Clinical, animal, and cell culture studies support the concept that these local RASs can act in an autocrine, paracrine, and/or intracrine manner.

Mechanisms of Disease: local renin–angiotensin–aldosterone systems and the pathogenesis and treatment of cardiovascular disease

  • R. Re
  • Biology, Medicine
    Nature Clinical Practice Cardiovascular Medicine
  • 2004
TLDR
Evidence points to the conclusion that the RAASs are complexly regulated, multifunctional systems with important roles both within and outside the cardiovascular system.

Mechanical stretch and angiotensin II differentially upregulate the renin-angiotensin system in cardiac myocytes In vitro.

TLDR
Results indicate that mechanical stretch in vitro upregulates both mRNA and protein expression of RAS components specifically in cardiac myocytes, and components of the cardiac RAS are independently and differentially regulated by mechanical stretch and Ang II in neonatal rat cardiacMyocytes.

Blood pressure-independent cardiac hypertrophy induced by locally activated renin-angiotensin system.

TLDR
These mice develop myocardial hypertrophy without signs of fibrosis independently from the presence of hypertension, demonstrating that local Ang II production is important in mediating the hypertrophic response in vivo.

Local renin-angiotensin systems: the unanswered questions.

  • A. Danser
  • Biology
    The international journal of biochemistry & cell biology
  • 2003

Distinct roles for the kidney and systemic tissues in blood pressure regulation by the renin-angiotensin system.

TLDR
It is demonstrated that regulation of blood pressure by extrarenal AT(1A) receptors cannot be explained by altered aldosterone generation, which suggests that AT( 1) receptor actions in systemic tissues such as the vascular and/or the central nervous systems make nonredundant contributions to blood pressure regulation.

Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney

TLDR
The findings demonstrate the critical role of the kidney in the pathogenesis of hypertension and its cardiovascular complications and suggest that the major mechanism of action of RAS inhibitors in hypertension is attenuation of angiotensin II effects in the kidney.

Mechanism of High Glucose–Induced Angiotensin II Production in Rat Vascular Smooth Muscle Cells

TLDR
Data suggest that polyol pathway metabolites and AGE can stimulate rat vascular chymase activity via ERK1/2 activation and increase Ang II production and contributes to increased accumulation of Ang II in vascular smooth muscle cells by HG.
...