A Focus on the Pathophysiology of Adrenomedullin Expression: Endothelitis and Organ Damage in Severe Viral and Bacterial Infections

Cells, Journal Year: 2024, Volume and Issue: 13(11), P. 892 - 892

Published: May 22, 2024

Adrenomedullin (ADM) is a peptide hormone produced primarily in the adrenal glands, playing crucial role various physiological processes. As well as improving vascular integrity and decreasing permeability, ADM acts vasodilator, positive inotrope, diuretic, natriuretic bronchodilator, antagonizing angiotensin II by inhibiting aldosterone secretion. also has antihypertrophic, anti-apoptotic, antifibrotic, antioxidant, angiogenic immunoregulatory effects antimicrobial properties. expression upregulated hypoxia, inflammation-inducing cytokines, viral or bacterial substances, strength of shear stress, leakage blood vessels. These pathological conditions are established during systemic inflammation that can result from infections, surgery, trauma/accidents burns. The ability to rapidly identify infections prognostic, predictive power makes it valuable tool severe burdened high incidence mortality. This review sheds light on pathophysiological processes cause endothelitis up development organ damage, resulting increase levels dosed through its more stable mid-regional proadrenomedullin (MR-proADM), most significant studies attest diagnostic prognostic accuracy highlighting severity appropriate therapeutic insights.

Language: Английский

---

Cellular and Mitochondrial Pathways Contribute to SGLT2 Inhibitors-mediated Tissue Protection: Experimental and Clinical Data

Current Pharmaceutical Design, Journal Year: 2024, Volume and Issue: 30(13), P. 969 - 974

Published: March 29, 2024

Abstract: In metabolic syndrome and diabetes, compromised mitochondrial function emerges as a critical driver of cardiovascular disease, fueling its development persistence, culminating in cardiac remodeling adverse events. this context, angiotensin II - the main interlocutor renin-angiotensin-aldosterone system promotes local systemic oxidative inflammatory processes. To highlight, low activity/expression proteins called sirtuins negatively participates these processes, allowing more significant imbalance, which impacts cellular tissue responses, causing damage, inflammation, vascular remodeling. The reduction energy production mitochondria has been widely described element all types disorders. Additionally, high sirtuin levels AMPK signaling stimulate hypoxia-inducible factor 1 beta promote ketonemia. Consequently, enhanced autophagy mitophagy advance through cells, sweeping away debris silencing orchestra stress ultimately protecting vulnerable from damage. highlight particular interest, SGLT2 inhibitors (SGLT2i) profoundly influence mechanisms. Randomized clinical trials have evidenced compelling picture SGLT2i emerging game-changers, wielding their power to demonstrably improve slash rates renal Furthermore, driven by recent evidence, emerge supermolecules, exerting beneficial actions increase efficiency, alleviate stress, curb severe inflammation. Its strengthen tissues create resilient defense against disease. conclusion, like treasure chest brimming with untold riches, on holds potential for health. Unlocking secrets, map guiding adventurers hidden promises pave way even potent therapeutic strategies.

Language: Английский

---

Pyruvate kinase M2 sustains cardiac mitochondrial integrity in septic cardiomyopathy by regulating PHB2-dependent mitochondrial biogenesis

International Journal of Medical Sciences, Journal Year: 2024, Volume and Issue: 21(6), P. 983 - 993

Published: Jan. 1, 2024

Previous studies have highlighted the protective effects of pyruvate kinase M2 (PKM2) overexpression in septic cardiomyopathy.In our study, we utilized cardiomyocyte-specific PKM2 knockout mice to further investigate role attenuating LPS-induced myocardial dysfunction, focusing on mitochondrial biogenesis and prohibitin 2 (PHB2).Our findings confirmed that deletion cardiomyocytes significantly exacerbated as evidenced by impaired contractile function relaxation.Additionally, intensified inflammation.At molecular level, LPS triggered characterized reduced ATP production, compromised respiratory complex I/III activities, increased ROS production.Intriguingly, absence worsened damage.Our investigations revealed disrupted cardiomyocytes, a disruption was PKM2.Given PHB2 is known downstream effector PKM2, employed adenovirus restore levels.The normalized biogenesis, restored integrity, promoted function.Overall, results underscore critical regulating progression cardiomyopathy.PKM2 deficiency impeded leading inflammation, cardiac function.The mitigated deleterious deletion.This discovery offers novel insight into mechanisms underlying cardiomyopathy suggests potential therapeutic targets for intervention.

Language: Английский

---

Sepsis-induced cardiac dysfunction: mitochondria and energy metabolism

Intensive Care Medicine Experimental, Journal Year: 2025, Volume and Issue: 13(1)

Published: Feb. 18, 2025

Abstract Sepsis is a life-threatening multi-organ dysfunction syndrome caused by dysregulated host response to infection, posing significant global healthcare challenge. Sepsis-induced myocardial (SIMD) common complication of sepsis, significantly increasing mortality due its high energy demands and low compensatory reserves. The substantial mitochondrial damage rather than cell apoptosis in SIMD suggests disrupted cardiac metabolism as crucial pathophysiological mechanism. Therefore, we systematically reviewed the mechanisms underlying SIMD, including alterations substrates, excitation–contraction coupling processes, dysfunction, autophagy biogenesis, summarizing potential therapeutic targets within them.

Language: Английский

---

Sepsis induces the cardiomyocyte apoptosis and cardiac dysfunction through activation of YAP1/Serpine1/caspase-3 pathway

Open Medicine, Journal Year: 2024, Volume and Issue: 19(1)

Published: Jan. 1, 2024

Sepsis triggers myocardial injury and dysfunction, leading to a high mortality rate in patients. Cardiomyocyte apoptosis plays positive regulatory role septic dysfunction. However, the mechanism is unclear.

Language: Английский

---