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Cyclic Nucleotide-Directed Protein Kinases in Cardiovascular Inflammation and Growth
Nathan A Holland1, Jake T Francisco2, Sean C Johnson3
1Department of Physiology, Brody School of Medicine, East Carolina University, 600 Moye Boulevard, Greenville, NC 27834, USA. hollandn17@ecu.edu.
Insights
Cardiovascular diseases (CVD) are a leading cause of death. Cyclic nucleotide-dependent protein kinases, like PKA and PKG, are crucial in managing heart and vascular disease, offering new therapeutic avenues.
Area of Science:
- Cardiovascular science
- Molecular biology
- Biochemistry
Background:
- Cardiovascular disease (CVD) is the leading global cause of mortality, claiming millions of lives annually.
- Despite extensive research, CVD prevalence continues to rise, necessitating novel therapeutic targets.
- Cyclic nucleotide pathways, involving cyclic AMP and cyclic GMP, play critical roles in cardiovascular homeostasis and disease pathogenesis.
Purpose of the Study:
- To review the current understanding of cyclic nucleotide-driven serine/threonine protein kinases in cardiovascular disease (CVD).
- To emphasize the roles of cyclic AMP-dependent protein kinase (PKA) and cyclic GMP-dependent protein kinase (PKG) in CVD.
- To explore the interactions of these kinases with inflammatory signals, receptors, and transcriptional pathways in CVD.
Main Methods:
- Literature review focusing on cyclic nucleotide-directed protein kinases in cardiovascular disease.
- Analysis of regulatory interactions between PKA, PKG, inflammatory components (e.g., interleukin-6), G protein-coupled receptors, growth factors, and transcriptional pathways.
- Synthesis of current knowledge on the role of these kinases in cardiovascular pathologies.
Main Results:
- Cyclic AMP and cyclic GMP, through their downstream kinases PKA and PKG, are integral to cardiovascular function and dysfunction.
- These kinases interact with key signaling pathways, including inflammatory signals, G protein-coupled receptors, and growth factor signaling, influencing CVD.
- The regulatory interplay between cyclic nucleotide-dependent kinases and transcriptional platforms is critical in the development of cardiovascular disease.
Conclusions:
- Cyclic nucleotide-dependent protein kinases (PKA and PKG) are pivotal regulators in cardiovascular disease.
- Understanding these kinases' interactions with inflammatory and signaling pathways is crucial for developing novel CVD therapies.
- Continued basic and clinical research into cyclic nucleotide-directed protein kinases is essential for advancing cardiac and vascular disease treatment.
Abstract:
Cardiovascular disease (CVD), including myocardial infarction (MI) and peripheral or coronary artery disease (PAD, CAD), remains the number one killer of individuals in the United States and worldwide, accounting for nearly 18 million (>30%) global deaths annually. Despite considerable basic science and clinical investigation aimed at identifying key etiologic components of and potential therapeutic targets for CVD, the number of individuals afflicted with these dreaded diseases continues to rise. Of the many biochemical, molecular, and cellular elements and processes characterized to date that have potential to control foundational facets of CVD, the multifaceted cyclic nucleotide pathways continue to be of primary basic science and clinical interest. Cyclic adenosine monophosphate (cyclic AMP) and cyclic guanosine monophosphate (cyclic GMP) and their plethora of downstream protein kinase effectors serve ubiquitous roles not only in cardiovascular homeostasis but also in the pathogenesis of CVD. Already a major target for clinical pharmacotherapy for CVD as well as other pathologies, novel and potentially clinically appealing actions of cyclic nucleotides and their downstream targets are still being discovered. With this in mind, this review article focuses on our current state of knowledge of the cyclic nucleotide-driven serine (Ser)/threonine (Thr) protein kinases in CVD with particular emphasis on cyclic AMP-dependent protein kinase (PKA) and cyclic GMP-dependent protein kinase (PKG). Attention is given to the regulatory interactions of these kinases with inflammatory components including interleukin 6 signals, with G protein-coupled receptor and growth factor signals, and with growth and synthetic transcriptional platforms underlying CVD pathogenesis. This article concludes with a brief discussion of potential future directions and highlights the importance for continued basic science and clinical study of cyclic nucleotide-directed protein kinases as emerging and crucial controllers of cardiac and vascular disease pathologies.
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