Foreword

Inflammation can arise in response to a variety of stimuli, including infectious agents, tissue injury (including DNA damage), and autoimmune diseases. Some of these responses are acute and the condition resolves, while others become chronic and exert a sustained impact on the host. For example, chronic inflammation triggers cellular events that can promote the malignant transformation of cells, or carcinogenesis. Moreover, chronic inflammation causes tissue remodeling, leading to the development of several cardiovascular diseases including atherosclerosis, myocardial infarction, and cardiac failure. Several inflammatory mediators, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, transforming growth factor (TGF)-β, and IL-10, have been shown to participate in stemming both the initiation and progression of several diseases. Moreover, recent increasing evidence indicates that cells of both the innate and the adaptive immune system, consisting of toll-like receptors (TLRs) and nucleotide binding oligomerization domain-like receptors (NLR), play a crucial role in the inflammation-induced pathogenesis and tissue remodeling of several diseases. The Current Topics section in this issue of the Biological and Pharmaceutical Bulletin consists of four reviews and one communication article focused on the roles of inflammation and tissue remodeling in disease, and present both as potential therapeutic targets.

Several recent studies have demonstrated that deletion of the NLR family (NLR: NOD-like receptors/nucleotide-binding oligomerization domain-like receptors) pyrin domain containing 3 inflammasomes (NLRP3) reduces inflammation, leading to the improvement of cardiac dysfunction and to remodeling in rodent models of myocardial infarction. Furthermore, the recent CANTOS trial (Canakinumab Antiinflammatory Thrombosis Outcome Study) revealed the efficacy of IL-1β inhibition in preventing recurrent cardiovascular events in patients with myocardial infarction. The first review, “Role of NLRP3 Inflammasome in Cardiac Inflammation and Remodeling after Myocardial Infarction” by Dr. Masafumi Takahashi, focuses on the roles of inflammation, as determined by NLRP3 inflammasomes, in the pathophysiology of myocardial infarction, including cardiac remodeling, and presents a new therapeutic approach.

Recently, implantation of several cell types into the myocardium has been performed as a treatment for myocardial infarction. Thus, the second review, “Therapeutic Potential of Pluripotent Stem Cells for Cardiac Repair after Myocardial Infarction” by Dr. Satomi Okano and Dr. Yuji Shiba, provides an overview of the present state of pluripotent stem cell (PSC)-based heart regeneration, and highlights the remaining hurdles. The authors show the importance of inflammation suppression in the breakthrough of PSC implantation for cardiac repair after myocardial infarction.

Dr. Ishida et al. contributed the third review, entitled “DNA Damage and Senescence-Associated Inflammation in Cardiovascular Disease.” Recent studies have revealed that a persistent DNA damage response triggers the induction of cell senescence and a senescence-associated secretory phenotype (SASP), which secretes numerous proinflammatory cytokines, chemokines, and growth factors.

As mentioned above, inflammation can arise in response to a variety of stimuli. “Inflammation and Temporomandibular Joint Derangement” by Dr. Ibi is the fourth review article included in this BPB review. Temporomandibular disorders are a common stomatognathic condition found across multiple generations. Patients with internal derangement or osteoarthritis of the temporomandibular joint (TMJ) often have TMJ synovitis, leading to the secretion of many inflammatory cytokines from TMJ synoviocytes. The molecular mechanisms underlying inflammation in temporomandibular disorders, and TMJ disorders as a therapeutic target, are presented and discussed.

Finally, the article “IL-1β Plays an Important Role in Pressure Overload-Induced Atrial Fibrillation in Mice” has been provided by Dr. Matsushita et al. The relationship between chronic inflammation and atrial fibrillation (AF) is well known. Moreover, hypertension is a risk for AF, and is known to induce cardiac inflammation. Recent evidence indicates that pressure overload-induced ventricular structural remodeling is associated with the activation of NLRP3 inflammasomes, including the apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC). Matsushita et al. studied the roles of NLRP3 inflammasomes in the development of hypertension-induced AF using mice with the deletion of either ASC or IL-1β genes, and provided evidence that the IL-1β activation pathway, distinct from NLRP3 inflammasomes, played an important role in pressure overload-induced sustained AF.

These articles provide a better understanding of the relationship between disease and inflammation, and will lead to further discoveries of potential therapeutic targets. The editor of this Current Topics thanks all the authors for their valuable contributions.