Since the first identification of renin by Tigerstedt and Bergmann in 1898, the renin-angiotensin system (RAS) has been extensively studied. The current view of the system is characterized by an increased complexity, as evidenced by the discovery of new functional components and pathways of the RAS. In recent years, the pathophysiological implications of the system have been the main focus of attention, and inhibitors of the RAS such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin (ANG) II receptor blockers have become important clinical tools in the treatment of cardiovascular and renal diseases such as hypertension, heart failure, and diabetic nephropathy. Nevertheless, the tissue RAS also plays an important role in mediating diverse physiological functions. These focus not only on the classical actions of ANG on the cardiovascular system, namely, the maintenance of cardiovascular homeostasis, but also on other functions. Recently, the research efforts studying these noncardiovascular effects of the RAS have intensified, and a large body of data are now available to support the existence of numerous organ-based RAS exerting diverse physiological effects. ANG II has direct effects at the cellular level and can influence, for example, cell growth and differentiation, but also may play a role as a mediator of apoptosis. These universal paracrine and autocrine actions may be important in many organ systems and can mediate important physiological stimuli. Transgenic overexpression and knock-out strategies of RAS genes in animals have also shown a central functional role of the RAS in prenatal development. Taken together, these findings may become increasingly important in the study of organ physiology but also for a fresh look at the implications of these findings for organ pathophysiology.

Physiology of local renin-angiotensin systems.

cAMP plays crucial roles in cardiac remodeling and the progression of heart failure Recently, we found that expression of cAMP hydrolyzing phosphodiesterase 3A (PDE3A) was significantly reduced in human failing hearts, accompanied by up-regulation of inducible cAMP early repressor (ICER) expression Angiotensin II (Ang II) and the β-adrenergic receptor agonist isoproterenol (ISO) also induced persistent PDE3A down-regulation and concomitant ICER up-regulation in vitro, which is important in Ang II- and ISO-induced cardiomyocyte apoptosis We hypothesized that interactions between PDE3A and ICER may constitute an autoregulatory positive feedback loop (PDE3A-ICER feedback loop), and this loop would cause persistent PDE3A down-regulation and ICER up-regulation Here, we demonstrate that ICER induction repressed PDE3A gene transcription PDE3A down-regulation activated cAMP/PKA signaling, leading to ICER up-regulation via PKA-dependent stabilization of ICER With respect to Ang II, the initiation of the PDE3A-ICER feedback loop depends on activation of Ang II type 1 receptor (AT1R), classical PKC(s), and CREB (cAMP response element binding protein) We further show that the PDE3A-ICER feedback loop is essential for Ang II-induced cardiomyocyte apoptosis ISO and PDE3 inhibitors also induced the PDE3A-ICER feedback loop and subsequent cardiomyocyte apoptosis, highlighting the importance of this PDE3A-ICER feedback loop and cAMP signaling in cardiomyocyte apoptosis Our findings may provide a therapeutic paradigm to prevent cardiomyocyte apoptosis and the progression of heart failure by inhibiting the PDE3A-ICER feedback loop

https://www.pnas.org/content/pnas/102/41/14771.full.pdf

A positive feedback loop of phosphodiesterase 3 (PDE3) and inducible cAMP early repressor (ICER) leads to cardiomyocyte apoptosis

Background Our previous studies have demonstrated that Ang II induced IGF-II and IGF-II R via ERK and JNK signaling pathways and further induces cardiac cell apoptosis. Purpose The present study investigates the protective role of alpinate Oxyphyllae fructus (AOF; Alpinia oxyphylla Miq) extracts on angiotensin II (Ang II)-stimulated H9c2 cardiomyoblast cells. Methods Western blotting was used to analyze the molecular mechanism involved in Ang II-treated H9c2 cells. Results AOF inhibits cardiac hypertrophy, apoptosis, mitochondrial dysfunction, and cardiac remodeling in Ang II-treated H9c2 cells. Conclusion All these data collectively suggest us that, AOF significantly inhibits Ang-II induced H9c2 cells apoptosis by suppressing the mitochondrial apoptotic pathway.

Inhibitory effect of alpinate Oxyphyllae fructus extracts on Ang II-induced cardiac pathological remodeling-related pathways in H9c2 cardiomyoblast cells

Elevations in angiotensin II (AngII) and transforming growth factor (TGF-β1) levels are often found under conditions leading to progression of heart failure. From several studies, it is evident that AngII enhances TGF-β1 expression via activator protein 1 (AP-1) activation, and that this pathway is involved in hypertrophic growth of the heart muscle and in the development of cardiac fibrosis. We now continued characterization of the signaling pathway stimulated by AngII in ventricular cardiomyocytes of rat and analyzed if the enhancement of TGF-β1 expression by AngII may also contribute to apoptosis induction, which is another predictor of heart failure progression. Stimulation of cardiomyocytes with 100 nM AngII for 2 h activated the transcription factors AP-1 and GATA by 68.6±23.9 or 70.7±9.8%. Induction of both factors was mediated by p38 mitogen-activated protein kinase (MAPK) because it was totally blocked using a specific inhibitor of the kinase (SB202190). When GATA was inhibited by transformation of cardiomyocytes with decoy oligonucleotides, AngII could not enhance TGF-β1 expression. This inhibition was observed on the mRNA level in real-time polymerase chain reaction and on the protein level in Western blots. As a consequence, upon AngII stimulation for 24 h, release of TGF-β1 from cardiomyocytes was also reduced from 240.5±50.4 to 130.5±22.1% (p<0.05). In contrast to the early induction of GATA and AP-1, the transcription factor similar to mothers against decapentaplegic homolog (SMAD) was induced by AngII after 24 h. This stimulation was dependent on TGF-β1 because it was blocked by antibodies specific for TGF-β1. Twenty-four hours after AngII addition, the number of apoptotic cardiomyocytes increased by 6.5±1.2%, and this apoptosis induction was blocked when SMAD activity was inhibited by transformation of cardiomyocytes with SMAD decoy oligonucleotides. In conclusion, the transcription factors AP-1 and GATA are activated by p38 MAPK upon AngII stimulation, and both are needed to enhance TGF-β1 expression in ventricular cardiomyocytes. TGF-β1 acts in an autocrine loop on the cells to induce apoptosis via SMAD signaling. Thus, the often-found correlation between AngII, TGF-β1, AP-1, and SMAD in pathogenesis of heart disease reflects the proapoptotic signaling pathway induced by AngII in cardiomyocytes.

Angiotensin II stimulates apoptosis via TGF-β1 signaling in ventricular cardiomyocytes of rat

Background: Cell death constitutes one of the key events in biology. Historically, apoptosis and necrosis have been considered to represent the 2 fundamental forms of cell death. Apoptosis is a tightly regulated, energy-dependent process in which cell death follows a programmed set of events. Necrosis refers to the sum of degenerative changes that follow any type of cell death. Methods and Results: The role of apoptosis in development of ischemic heart disease, hypertensive heart disease, and end-stage heart failure has been well documented. Recent evidence suggests the potential role of a third mechanism of cell death, autophagy, in loss of cardiac myocytes. Autophagic cell death has been recently documented in myocardial cells from hypertrophied, failing, and hibernating myocardium. Conclusion: In this review, we will list the basic mechanisms of apoptosis and autophagic cell death and examine the recent developments in apoptosis and autophagic cell death as it pertains to cardiovascular disease. Cell death constitutes one of the key events in biology. Cellular homeostasis is maintained by a balance between the increase (by differentiation from precursors and by proliferation), and decrease (by further differentiation and cell death) in the number of a cell population. Our understanding of the mechanisms of cell death has vastly increased in the last 30 years with advances in molecular genetics and cell biology. The concept of cell death can be found in texts dating back to the rime of Galen around 200 AD. Virchow, in 1858, described what he called degeneration, necrosis, and mortification as a passive process. In 1885, Fleming introduced the idea of spontaneous cell death, by first observing epithelial cell nuclei in regressing ovarian follicles that appeared to be breaking apart. In 1910, von Recklinghausen described cell death accompanied by swelling in bone cells, and coined the term oncosis.

Review Article ''How Do Cardiomyocytes Die?'' Apoptosis and Autophagic Cell Death in Cardiac Myocytes

Angiotensin II (ANG II) via AT1 receptors induces apoptosis in cardiomyocytes in vitro. We tested the hypothesis that in vivo AT1 receptor stimulation is accompanied by cardiac apoptosis and attemp...

https://www.physiology.org/doi/pdf/10.1152/ajpheart.00984.2001

Effect of AT1 receptor blockade on cardiac apoptosis in angiotensin II-induced hypertension

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Ping Yue

Author Tools

Chat about Author

Papers

Effect of AT1 receptor blockade on cardiac apoptosis in angiotensin II-induced hypertension