Invitation to New Highlights in Cardiovascular Diseases
Cardiovascular diseases including heart failure and cerebrovascular disease rank as the second most morbidity and mortality in the developed countries. Considering the severity of heart failure symptom and disease progresses of the patients affected, the many researchers in the academia and pharmaceutical companies are eager to find more effective and safer approaches to overcome the diseases. Recent development of diagnostic approaches at ‘state-of-art’ levels as well as the intensive meta-analysis of clinical data has led to the novel concepts of diseases. Moreover, recent progresses in the cardiac research fields have been explosively expanded and have shown that many cellular components in the heart other than cardiomyocytes and vascular tissues also significantly contribute to the mechanisms of the cardiovascular diseases. Thus, we believe that the review series on the cardiovascular diseases and their pathophysiologies are timely and mandatory. For this special issue series of cardiovascular diseases, we invited four review articles on the implications of macrophages and mitochondria in the hearts. In addition, the new disease models regarding aortic aneurysm and heart failure with preserved ejection fraction were introduced. We believe that this special issue will draw much interest from students, researchers, pharmaceutical companies, and even from the health communities engaged in fighting against cardiovascular diseases.
The human heart may be coaxed toward regeneration by modifying the activity of specialized immune cells known as macrophages. Insight from the regenerating hearts of zebrafish, newt, and neonatal mammals has revealed that macrophages are required to replace scar with functioning heart tissue. As mammals lose the ability to regenerate heart tissue, macrophages mature from a regenerative phenotype towards an immunomodulatory phenotype. By adulthood, heart macrophages comprise a mixed population of cells arising from either early embryonic development or differentiation from white blood cells. In this issue, Dr. Geoffrey de Couto from the Smidt Heart Institute at Cedars-Sinai Medical Center, reviews the role of macrophages in heart repair and therapeutic strategies to enhance their activity. Recent studies suggest that exosomes, which are naturally-released nano-sized vesicles, can re-educate adult macrophages to protect the heart from injury.
A review of aneurysm formation, swelling in blood vessel, in the aorta, examines distinctions between two forms of the condition and the role of proteins in the extracellular matrix which surrounds cells of the arterial wall. Rupture of aneurysms in the aorta, the body’s main artery, is a major cause of death. Researchers led by Zamaneh Kassiri at the University of Alberta, Edmonton, Canada, emphasize that aneurysms in the thoracic and abdominal regions of the aorta are distinct conditions with crucial differences in their causes. Disrupted production and assembly of the extracellular matrix and its proteins may underlie thoracic aneurysm formation. Factors triggering the degradation of extracellular matrix proteins may be more significant in abdominal aneurysms. Understanding the differing molecular mechanisms involved could help address the current lack of effective drug treatments for these dangerous conditions.
The condition known as heart failure with preserved ejection fraction (HFpEF), in which the fraction of blood pumped from the heart by each heartbeat remains near normal is an increasing cause of illness and death. Available treatments are unsatisfactory. Heart functions also appears normal or near normal in echocardiography imaging, but patients suffer some typical symptoms of heart failure including shortness of breath, excessive tiredness, and reduced ability to exercise. Gwang Hyeon Eom and Somy Yoon at Chonnam National University in Gwangju, South Korea, review understanding of the causes and clinical features of HFpEF, and the development of animal models to aid research into the condition. Studies in rodents are revealing molecular level cellular changes that may be involved in causing HFpEF. The insights gained will hopefully lead to more effective treatments.
Heart disease progression could be tackled by targeting signaling molecules that cause oxidative stress. Jennifer Kwong at Emory University School of Medicine in Atlanta, USA, and co-workers reviewed research into the role of mitochondria and their associated signaling molecules in the development of heart disease. Mitochondria are a major source of reactive oxygen species (ROS), signaling molecules involved in muscle contraction and calcium transfer in the heart, but they also destroy ROS to maintain a balance. Disruption to this balance can lead to elevated ROS, causing DNA and cellular damage, triggering disease. Animal trials using drugs to target mitochondrial ROS show promise in limiting heart disease progression. Further research is needed to determine whether this approach will work in humans and which specific heart problems might benefit from such therapies.