Joseph Adu-Amankwaah

Autophagy is an essential cellular process that maintains homeostasis, regulates organelle turnover, preserves energy balance, and ensures protein quality control. Central to autophagy regulation is calcium (Ca²⁺) signaling, which integrates inputs from multiple Ca²⁺ channels and handling proteins, including L-type and T-type voltage-gated Ca²⁺ channels, transient receptor potential mucolipin (TRPML) channels, inositol 1,4,5-trisphosphate receptors (IP3Rs), ryanodine receptors (RyRs), the mitochondrial calcium uniporter (MCU), sodium-calcium exchangers (NCX), sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA), and calcium/calmodulin-dependent protein kinase II (CaMKII). Although these regulators are well studied, their disease-specific functions remain context-dependent and complex. In cancer, Ca²⁺-regulated autophagy enhances metabolic flexibility, maintains mitochondrial integrity, promotes resistance to chemotherapy, and facilitates immune evasion, thereby supporting tumor growth and survival. Conversely, in cardiovascular diseases (CVDs), autophagy enables cardiomyocytes to adapt to ischemic, inflammatory, and hemodynamic stress. However, dysregulated Ca²⁺ signaling and impaired autophagic flux contribute to tumor progression and pathological cardiac remodeling, respectively. This review explores the molecular mechanisms underlying Ca²⁺-dependent autophagy in cancer and CVDs, providing a detailed analysis of shared signaling pathways and potential therapeutic targets. Discussed in this review, the emerging field of cardio-oncology highlights a mechanistic convergence in which anticancer therapies disrupt cardiomyocyte Ca²⁺ homeostasis, causing mitochondrial Ca²⁺ overload, ER stress, and defective autophagy, ultimately leading to cardiotoxicity, while tumor cells exploit the same pathways to survive therapeutic stress. By elucidating the spatiotemporal dynamics of Ca²⁺ signaling and autophagy, we identify common molecular hubs and propose precision strategies to enhance anticancer efficacy while preserving cardiac function, advancing translational innovation in cardio-oncology.

Cardiovascular diseases (CVDs) represent a leading cause of global mortality. Myocardial fibrosis (MF), a common pathological hallmark in CVDs, signifies disease progression to severe stages. Its pathogenesis is highly complex, with autophagy playing a pivotal regulatory role. This narrative review synthesizes and critically evaluates the current literature to elucidate the interplay between MF and autophagy. The focus lies on systematically examining the molecular mechanisms and key signaling pathways involved in autophagy-mediated regulation of MF. We systematically examine key molecular pathways and components through which autophagy regulates MF, including mitophagy, the NLRP3 inflammasome, FOXO signaling, the ULK1 complex, the mTOR pathway, and TGF-β signaling. These pathways collectively influence fibroblast activation, collagen metabolism, and overall cardiac ECM remodeling. Autophagy serves as a crucial modulator of MF through multiple interconnected molecular pathways. Targeting specific nodes within the autophagic process holds significant therapeutic promise for mitigating MF and slowing CVD progression. This review consolidates current understanding and highlights novel insights, underscoring the need for further research to translate these mechanisms into effective clinical interventions.

Joseph Adu-Amankwaah, MLS, PhD; Behind the shadows: Bringing the cardiovascular secrets of long COVID into light, European Journal of Preventive Cardiology, , z

The intricate web of cancer biology is governed by the active participation of long non-coding RNAs (lncRNAs), playing crucial roles in cancer cells' proliferation, migration, and drug resistance. Pioneering research driven by machine learning algorithms has unveiled the profound ability of specific combinations of lncRNAs to predict the prognosis of cancer patients. These findings highlight the transformative potential of lncRNAs as powerful therapeutic targets and prognostic markers. In this comprehensive review, we meticulously examined the landscape of lncRNAs in predicting the prognosis of the top five cancers and other malignancies, aiming to provide a compelling reference for future research endeavours. Leveraging the power of machine learning techniques, we explored the predictive capabilities of diverse lncRNA combinations, revealing their unprecedented potential to accurately determine patient outcomes.

Colorectal cancer (CRC) is a significant contributor to cancer mortality worldwide, and the presence of cancer stem cells (CSC) represents a major challenge for achieving effective treatment. miRNA...

Stress-induced cardiovascular diseases characterized by inflammation are among the leading causes of morbidity and mortality in postmenopausal women worldwide. Estradiol (E2) is known to be cardioprotective via the modulation of inflammatory mediators during stress. But the mechanism is unclear. TNFα, a key player in inflammation, is primarily converted to its active form by 'A Disintegrin and Metalloprotease 17' (ADAM17). We investigated if E2 can regulate ADAM17 during stress. Experiments were performed using female FVB wild-type (WT), C57BL/6 WT, and G protein-coupled estrogen receptor 1 knockout (GPER-1 KO) mice and H9c2 cells. The study revealed a significant increase in cardiac injury and inflammation during isoproterenol (ISO)-induced stress in ovariectomized (OVX) mice. Additionally, ADAM17’s membrane content (mADAM17) was remarkably increased in OVX and GPER-1 KO mice during stress. However, in vivo supplementation of E2 significantly reduced cardiac injury, mADAM17, and inflammation. Also, administering G1 (GPER-1 agonist) in mice under stress reduced mADAM17. Further experiments demonstrated that E2, via GPER-1/PI3K pathway, localized ADAM17 at the perinuclear region by normalizing β1AR-Gαs, mediating the switch from β2AR-Gαi to Gαs, and reducing phosphorylated kinases, including p38 MAPKs and ERKs. Thus, using G15 and LY294002 to inhibit GPER-1 and its down signaling molecule, PI3K, respectively, in the presence of E2 during stress resulted in the disappearance of E2’s modulatory effect on mADAM17. In vitro knockdown of ADAM17 during stress significantly reduced cardiac injury and inflammation, confirming its significant inflammatory role. These interesting findings provide novel evidence that E2 and G1 are potential therapeutic agents for ADAM17-induced inflammatory diseases associated with postmenopausal females.

G protein-coupled receptor kinase 2 (GRK2) is a multifunctional protein involved in regulating G protein-coupled receptor (GPCR) and non-GPCR signaling in the body. In the cardiovascular system, increased expression of GRK2 has been implicated in the occurrence and development of several cardiovascular diseases (CVDs). Recent studies have found gender differences in GRK2 in the cardiovascular system under physiological and pathological conditions, where GRK2’s expression and activity are increased in males than in females. The incidence of CVDs in premenopausal women is lower than in men of the same age, which is related to estrogen levels. Given the shared location of GRK2 and estrogen receptors, estrogen may interact with GRK2 by modulating vital molecules such as calmodulin (CaM), caveolin, RhoA, nitrate oxide (NO), and mouse double minute 2 homolog (Mdm2), via signaling pathways mediated by estrogen’s genomic (ERα and ERβ), and non-genomic (GPER) receptors, conferring cardiovascular protection in females. Highlighting the gender differences in GRK2 and understanding its interaction with estrogen in the cardiovascular system is pertinent in treating gender-related CVDs. As a result, this article explores the gender differences of GRK2 in the cardiovascular system and its relationship with estrogen during disease conditions. Estrogen’s protective and therapeutic effects and its mechanism on GRK2-related cardiovascular diseases have also been discussed.

Infective endocarditis (IE), characterized by inflammation of the endocardial surface of the heart and its valves, results from infections caused by Staphylococcus, Streptococcus and Acinetobacter ... Plain language summary Infective endocarditis (IE), known as inflammation of the thin membrane that lines the inside of the heart, results from infections from microbes (e.g., Staphylococcus, Strep...