The journal of cardiovascular aging最新文献

Age-associated cardiovascular disease is becoming progressively prevalent due to the increased lifespan of the population. However, the fundamental mechanisms underlying the aging process and the corresponding decline in tissue functions are still poorly understood. The heart has a very high energy demand and the cellular energy needed to sustain contraction is primarily generated by mitochondrial oxidative phosphorylation. Mitochondria are also involved in supporting various metabolic processes, as well as activation of the innate immune response and cell death pathways. Given the central role of mitochondria in energy metabolism and cell survival, the heart is highly susceptible to the effects of mitochondrial dysfunction. These key organelles have been implicated as underlying drivers of cardiac aging. Here, we review the evidence demonstrating the mitochondrial contribution to the cardiac aging process and disease susceptibility. We also discuss the potential mechanisms responsible for the age-related decline in mitochondrial function.

Heart failure (HF) is a complex and multifactorial disease. Recent advances have been made in understanding the underlying molecular processes involved in HF pathogenesis. These scientific advancements have brought to light the importance of the secretome. This paper presents a thorough overview of the state of science regarding the secretome's involvement in the onset, progression, and possibility of improved diagnosis and therapeutic interventions in HF. We explore the various types of secreted factors, including novel proteins, growth factors, cytokines, and microRNAs. We also discuss how they affect cellular signaling, angiogenesis, fibrosis, pathological cardiac remodeling, and inflammation in HF. Furthermore, we examine the role of the secretome in cardioprotection and cardiotoxicity. This review emphasizes the potential of the secretome for biomarker discovery. This might enable better HF diagnosis, risk stratification, monitoring and treatment. The review also discusses the difficulties on investigating the role of secreted factors and novel directions on secretome research. It highlights its potential as a target for novel therapeutic approaches and biomarker development.

Introduction: Heart failure (HF) is the leading cause of death worldwide. Most large and small animal disease models of HF are based on surgical procedures. A common surgical technique to induce HF is transverse aortic constriction (TAC), which induces pressure overload. The conventional TAC (cTAC) procedure is a highly invasive surgery that is associated with severe inflammation and excessive perioperative deaths.

Aim: To establish an improved, minimally invasive TAC (mTAC) procedure that does not require thoracotomy.

Methods and results: Following anesthesia, mice were intubated, and a small incision was made at the neck and chest. After cutting the sternum about 4 mm, the aortic arch was approached without opening the pleural cavity. A suture was placed between the brachiocephalic artery and the left common carotid artery. This model was associated with low perioperative mortality and a highly reproducible constriction evidenced by an increased right-to-left carotid blood flow velocity ratio in mTAC mice (5.9 ± 0.2) vs. sham controls (1.2 ± 0.1; P < 0.001). mTAC mice exhibited progressive cardiac remodeling during the 8 weeks post-TAC, resulting in reduced left ventricular (LV) contractility, increased LV end-systolic diameter, left atrial enlargement and diastolic dysfunction, and an increased heart weight to tibia length ratio (mTAC: 15.0 ± 0.8 vs. sham: 10.1 ± 0.6; P < 0.01).

Conclusion: Our data show that the mTAC procedure yields a highly reproducible phenotype consisting of LV contractile dysfunction and enlargement, combined with left atrial enlargement and diastolic dysfunction.

Potential impact of the findings: This model may be used to test the molecular mechanisms underlying atrial remodeling associated with HF development or to evaluate therapeutic strategies to treat these conditions.