| 1. |
- Barrett, Aidan, et al.
(författare)
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Physiological estrogen levels are dispensable for the sex difference in immune responses during allergen-induced airway inflammation
- 2023
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Ingår i: Immunobiology. - : Elsevier BV. - 0171-2985. ; 228:3
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Tidskriftsartikel (refereegranskat)abstract
- Women show an increased prevalence of adult-onset asthma compared to men and previous studies have shown that testosterone inhibits while estrogen worsens allergen-induced airway inflammation. However, detailed knowledge about the aggravating effects of estrogen on immune responses remain unclear. Defining the effects of physiological levels of estrogen on immune responses in asthma would aid in the development of improved treatment strategies.In this study, the importance of estrogen for the sex difference in asthma was determined using a murine model of house dust mite (HDM)-induced airway inflammation on intact female and male mice, as well as on ovariectomized (OVX) female mice treated with a physiological dose of 17 beta-estradiol (E2). Innate and adaptive immune responses were defined in bronchoalveolar lavage fluid, mediastinal lymph node (mLN) and lung tissue.The results reveal increased numbers of lung eosinophils, macrophages, and dendritic cells in female but not in male mice after HDM challenge. Females also exhibit higher numbers of Th17 cells in both mLN and lung in response to HDM. However, treatment of OVX mice with physiological levels of E2 does not influence any of the analyzed cell populations.Together, this study confirms the previously reported sex difference in allergen-induced airway inflammation and show that female mice mount stronger innate and adaptive immune responses to HDM challenge, but these effects are not mediated by physiological levels of E2.
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| 2. |
- Corciulo, Carmen, et al.
(författare)
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Physiological levels of estradiol limit murine osteoarthritis progression
- 2022
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Ingår i: Journal of Endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 255:2, s. 39-51
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Tidskriftsartikel (refereegranskat)abstract
- Among patients with knee osteoarthritis (OA), postmenopausal women are over-represented. The purpose of this study was to determine whether deficiency of female sex steroids affects OA progression and to evaluate the protective effect of treatment with a physiological dose of 17 beta-estradiol (E2) on OA progression using a murine model. Ovariectomy (OVX) of female mice was used to mimic a postmenopausal state. OVX or sham-operated mice underwent surgery for destabilization of the medial meniscus (DMM) to induce OA. E2 was administered in a pulsed manner for 2 and 8 weeks. OVX of OA mice did not influence the cartilage phenotype or synovial thickness, while both cortical and trabecular subchondral bone mineral density (BMD) decreased after OVX compared with sham-operated mice at 8 weeks post-DMM surgery. Additionally, OVX mice displayed decreased motor activity, reduced threshold of pain sensitivity, and increased number of T cells in the inguinal lymph nodes compared to sham-operated mice 2 weeks after OA induction. Eight weeks of treatment with E2 prevented cartilage damage and thickening of the synovium in OVX OA mice. The motor activity was improved after E2 replacement at the 2 weeks time point, which was also associated with lower pain sensitivity in the OA paw. E2 treatment protected against OVX-induced loss of subchondral trabecular bone. The number of T cells in the inguinal lymph nodes was reduced by E2 treatment after 8 weeks. This study demonstrates that treatment with a physiological dose of E2 exerts a protective role by reducing OA symptoms.
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| 3. |
- Drevinge, Christina, 1983, et al.
(författare)
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Treatment with a tissue-selective oestrogen complex does not affect disease pathology but reduces pre-BI cells in lupus-prone mice.
- 2024
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Ingår i: Scandinavian journal of rheumatology. - 1502-7732. ; 53:1, s. 49-58
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE or lupus) is an autoimmune disease characterized by B-cell dysfunction, production of autoantibodies, and immune complex formation. Lupus is overrepresented in females, indicating that sex hormones play a role in the pathophysiology. Treatment with a tissue-selective oestrogen complex (TSEC) containing conjugated oestrogens and the selective oestrogen receptor modulator bazedoxifene (BZA) protects against postmenopausal vasomotor symptoms and osteoporosis, but its impact on organ damage in lupus is not fully understood.We used ovariectomized MRL/lpr mice, treated with two different physiological doses of 17β-oestradiol-3-benzoate (E2), BZA, or TSEC (E2 plus BZA), to assess early and late B-cell development and to determine histological disease manifestations in the kidneys and salivary glands.TSEC treatment reduced the frequency of the pre-BI population in bone marrow to levels equivalent to treatment with physiological doses of E2 alone but did not affect any of the other examined B-cell populations. Our earlier studies indicated that TSEC treatment did not aggravate disease development in ovariectomized MRL/lpr mice, while protecting against trabecular bone loss. Here, we follow up on our previous study and show that neither ovariectomy alone nor TSEC treatment of ovariectomized MRL/lpr mice influenced perivascular lymphocyte infiltration to the kidneys or salivary glands.TSEC does not aggravate a mouse model of lupus, when given in doses that protect against postmenopausal lupus-associated bone loss. This indicates that further investigations into TSEC as a treatment for osteoporosis or vasomotor symptoms in postmenopausal women with SLE are warranted.
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| 4. |
- Scheffler, Julia M., et al.
(författare)
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ER alpha Signaling in a Subset of CXCL12-Abundant Reticular Cells Regulates Trabecular Bone in Mice
- 2022
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Ingår i: JBMR Plus. - : Wiley. - 2473-4039. ; 6:8
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen has pronounced effects on the immune system, which also influences bone homeostasis. In recent years, stromal cells in lymphoid organs have gained increasing attention as they not only support the regulation of immune responses but also affect bone remodeling. A conditional knockout mouse model where estrogen receptor alpha (ER alpha) is deleted in CCL19-expressing stromal cells (Ccl19-Cre ER alpha(fl/fl) mice) was generated and bone densitometry was performed to analyze the importance of stromal cell-specific ER alpha signaling on the skeleton. Results showed that female Ccl19-Cre ER alpha(fl/fl) mice display reduced total bone mineral density and detailed X-ray analyses revealed that ER alpha expression in CCL19-expressing stromal cells is important for trabecular but not cortical bone homeostasis. Further analysis showed that the trabecular bone loss is caused by increased osteoclastogenesis. Additionally, the bone formation rate was reduced; however, the expression of osteoprogenitor genes was not altered. Analysis of the bone marrow stromal cell compartment revealed a deletion of ER alpha in a subgroup of CXCL12-abundant reticular (CAR) cells resulting in increased secretion of the pro-osteoclastogenic chemokine CXCL12. In conclusion, this study reveals the importance of ER alpha signaling in CAR cells for bone health. (c) 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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| 5. |
- Scheffler, Julia M., et al.
(författare)
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Interleukin 17A: a Janus-faced regulator of osteoporosis
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin (IL)-17A is a well-described mediator of bone resorption in inflammatory diseases, and postmenopausal osteoporosis is associated with increased serum levels of IL-17A. Ovariectomy (OVX) can be used as a model to study bone loss induced by estrogen deficiency and the role of IL-17A in osteoporosis development has previously been investigated using various methods to inhibit IL-17A signaling in this model. However, the studies show opposing results. While some publications reported IL-17A as a mediator of OVX-induced osteoporosis, others found a bone-protective role for IL-17 receptor signaling. In this study, we provide an explanation for the discrepancies in previous literature and show for the first time that loss of IL-17A has differential effects on OVX-induced osteoporosis; with IL-17A being important for cortical but not trabecular bone loss. Interestingly, the decrease in trabecular bone after OVX in IL-17A knock-out mice, was accompanied by increased adipogenesis depicted by elevated leptin levels. Additionally, the bone marrow adipose tissue expanded, and the bone-turnover decreased in ovariectomized mice lacking IL-17A compared to ovariectomized WT mice. Our results increase the understanding of how IL-17A signaling influences bone remodeling in the different bone compartments, which isof importance for the development of new treatments of post-menopausal osteoporosis. © 2020, The Author(s).
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| 6. |
- Andersson, Linda, 1973, et al.
(författare)
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Deficiency in perilipin 5 reduces mitochondrial function and membrane depolarization in mouse hearts.
- 2017
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Ingår i: The international journal of biochemistry & cell biology. - : Elsevier BV. - 1878-5875 .- 1357-2725. ; 91:Pt A, s. 9-13
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Tidskriftsartikel (refereegranskat)abstract
- Myocardial triglycerides stored in lipid droplets are important in regulating the intracellular delivery of fatty acids for energy generation in mitochondria, for membrane biosynthesis, and as agonists for intracellular signaling. Previously, we showed that deficiency in the lipid droplet protein perilipin 5 (Plin5) markedly reduces triglyceride storage in cardiomyocytes and increases the flux of fatty acids into phospholipids. Here, we investigated whether Plin5 deficiency in cardiomyocytes alters mitochondrial function. We found that Plin5 deficiency reduced mitochondrial oxidative capacity. Furthermore, in mitochondria from Plin5((-/)(-)) hearts, the fatty acyl composition of phospholipids in mitochondrial membranes was altered and mitochondrial membrane depolarization was markedly compromised. These findings suggest that mitochondria isolated from hearts deficient in Plin5, have specific functional defects.
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| 7. |
- Cinato, Mathieu, et al.
(författare)
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Cardiac Plin5 interacts with SERCA2 and promotes calcium handling and cardiomyocyte contractility
- 2023
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Ingår i: Life Science Alliance. - : Life Science Alliance, LLC. - 2575-1077. ; 6:4
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Tidskriftsartikel (refereegranskat)abstract
- The adult heart develops hypertrophy to reduce ventricular wall stress and maintain cardiac function in response to an increased workload. Although pathological hypertrophy generally prog-resses to heart failure, physiological hypertrophy may be car-dioprotective. Cardiac-specific overexpression of the lipid-droplet protein perilipin 5 (Plin5) promotes cardiac hypertrophy, but it is unclear whether this response is beneficial. We analyzed RNA -sequencing data from human left ventricle and showed that car-diac PLIN5 expression correlates with up-regulation of cardiac contraction-related processes. To investigate how elevated cardiac Plin5 levels affect cardiac contractility, we generated mice with cardiac-specific overexpression of Plin5 (MHC-Plin5 mice). These mice displayed increased left ventricular mass and cardiomyocyte size but preserved heart function. Quantitative proteomics identified sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) as a Plin5-interacting protein. In situ proximity ligation assay further confirmed the Plin5/SERCA2 interaction. Live imaging showed in-creases in intracellular Ca2+ release during contraction, Ca2+ removal during relaxation, and SERCA2 function in MHC-Plin5 versus WT cardiomyocytes. These results identify a role of Plin5 in improving cardiac contractility through enhanced Ca2+ signaling.
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| 8. |
- Corciulo, Carmen, et al.
(författare)
-
Physiological levels of estradiol limit murine osteoarthritis progression
- 2022
-
Ingår i: The Journal of endocrinology. - 0022-0795 .- 1479-6805. ; 255:2, s. 39-51
-
Tidskriftsartikel (refereegranskat)abstract
- Among patients with knee osteoarthritis (OA), postmenopausal women are over-represented. The purpose of this study was to determine whether deficiency of female sex steroids affects OA progression and to evaluate the protective effect of treatment with a physiological dose of 17β-estradiol (E2) on OA progression using a murine model. Ovariectomy (OVX) of female mice was used to mimic a postmenopausal state. OVX or sham-operated mice underwent surgery for destabilization of the medial meniscus (DMM) to induce OA. E2 was administered in a pulsed manner for 2 and 8 weeks. OVX of OA mice did not influence the cartilage phenotype or synovial thickness, while both cortical and trabecular subchondral bone mineral density (BMD) decreased after OVX compared with sham-operated mice at 8 weeks post-DMM surgery. Additionally, OVX mice displayed decreased motor activity, reduced threshold of pain sensitivity, and increased number of T cells in the inguinal lymph nodes compared to sham-operated mice 2 weeks after OA induction. Eight weeks of treatment with E2 prevented cartilage damage and thickening of the synovium in OVX OA mice. The motor activity was improved after E2 replacement at the 2 weeks time point, which was also associated with lower pain sensitivity in the OA paw. E2 treatment protected against OVX-induced loss of subchondral trabecular bone. The number of T cells in the inguinal lymph nodes was reduced by E2 treatment after 8 weeks. This study demonstrates that treatment with a physiological dose of E2 exerts a protective role by reducing OA symptoms.
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| 9. |
- Corciulo, Carmen, et al.
(författare)
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Pulsed administration for physiological estrogen replacement in mice
- 2021
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Ingår i: F1000Research. - : F1000 Research Ltd. - 2046-1402 .- 1759-796X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Estrogens are important regulators of body physiology and have major effects on metabolism, bone, the immune- and central nervous systems. The specific mechanisms underlying the effects of estrogens on various cells, tissues and organs are unclear and mouse models constitute a powerful experimental tool to define the physiological and pathological properties of estrogens. Menopause can be mimicked in animal models by surgical removal of the ovaries and replacement therapy with 17β-estradiol in ovariectomized (OVX) mice is a common technique used to determine specific effects of the hormone. However, these studies are complicated by the non-monotonic dose-response of estradiol, when given as therapy. Increased knowledge of how to distribute estradiol in terms of solvent, dose, and administration frequency, is required in order to accurately mimic physiological conditions in studies where estradiol treatment is performed. In this study, mice were OVX and treated with physiological doses of 17β-estradiol-3-benzoate (E2) dissolved in miglyol or PBS. Subcutaneous injections were performed every 4 days to resemble the estrus cycle in mice. Results show that OVX induces an osteoporotic phenotype, fat accumulation and impairment of the locomotor ability, as expected. Pulsed administration of physiological doses of E2 dissolved in miglyol rescues the phenotypes induced by OVX. However, when E2 is dissolved in PBS the effects are less pronounced, possibly due to rapid wash out of the steroid.
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| 10. |
- Drevinge, Christina, 1983
(författare)
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Cardiac lipid storage and metabolism following myocardial ischemia
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Myocardial ischemia is associated with cellular- and metabolic adjustments within the heart, including accumulation of lipids. Myocardial lipids are stored in cytosolic droplets, consisting of a core of neutral lipids surrounded by a complex surface containing proteins, such as perilipins. Little is known about how myocardial lipid content and dynamics affect the function of the ischemic heart. In this study, we investigated cardiac lipid accumulation and the consequences of altered lipid storage and metabolism following myocardial ischemia. In Paper I, we investigated lipid accumulation of in a porcine model of ischemia/reperfusion and we found that cholesteryl esters accumulate in the myocardium following ischemia. The expression of the low density lipoprotein receptor (LDLr) and the low density lipoprotein receptor-related protein 1 (LRP1) was up-regulated, suggesting that cholesteryl ester uptake was mediated by these receptors. In Paper II, we investigated the role of the lipid droplet protein Perilipin 5 (Plin5) in the pathophysiology of myocardial ischemia. In humans, we showed that a polymorphism in the PLIN5 gene is associated with reduced heart function following myocardial ischemia. In mice, Plin5 deficiency dramatically reduced the triglyceride content in the heart. Under normal conditions, Plin5–/– mice maintained a close to normal heart function by decreasing fatty acid uptake and increasing substrate utilization from glucose, thus preserving the energy balance. However, during stress or myocardial ischemia, Plin5 deficiency resulted in reduced myocardial substrate availability, severely reduced heart function and increased mortality. In Paper III, we investigated the role of Plin2 in lipid storage and cardiac function following ischemia. We found that deficiency of Plin2 in mice surprisingly resulted in significantly increased levels of triglycerides. The heart function was not compromised in Plin2–/– mice in baseline and stress conditions. However, heart function was markedly reduced in Plin2–/– mice after induced myocardial infarction. In conclusion, our findings indicate that dysregulation of myocardial lipid metabolism and storage influences heart function and survival following myocardial ischemia. Furthermore, our findings highlight a role for lipid droplet proteins perilipins in cardioprotection following myocardial ischemia.
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| 11. |
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| 12. |
- Drevinge, Christina, 1983, et al.
(författare)
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Intermediate monocytes correlate with CXCR3(+) Th17 cells but not with bone characteristics in untreated early rheumatoid arthritis
- 2021
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 16:3
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Tidskriftsartikel (refereegranskat)abstract
- Background Rheumatoid arthritis (RA) is associated with development of generalized osteoporosis. Bone-degrading osteoclasts are derived from circulating precursor cells of monocytic lineage, and the intermediate monocyte population is important as osteoclast precursors in inflammatory conditions. T cells of various subsets are critical in the pathogenesis of both RA and associated osteoporosis, but so far, no studies have examined associations between circulating intermediate monocytes, T cell subsets and bone characteristics in patients with RA. The aim of this study was to investigate the frequency of intermediate monocytes in patients with untreated early rheumatoid arthritis (ueRA) compared to healthy controls (HC), and to explore the correlation between intermediate monocytes and a comprehensive panel of T helper cell subsets, bone density and bone microarchitecture in ueRA patients. Methods 78 patients with ueRA fulfilling the ACR/EULAR 2010 criteria were included and compared to 29 age- and sex-matched HC. Peripheral blood samples were obtained before start of treatment and proportions of monocyte subsets and CD4(+) helper and regulatory T cell subsets were analyzed by flow cytometry. Bone densitometry was performed on 46 of the ueRA patients at inclusion using DXA and HR-pQCT. Results Flow cytometric analyses showed that the majority of ueRA patients had frequencies of intermediate monocytes comparable to HC. The intermediate monocyte population correlated positively with CXCR3(+) Th17 cells in ueRA patients but not in HC. However, neither the proportions of intermediate monocytes nor CXCR3(+) Th17 cells were associated with bone density or bone microarchitecture measurements. Conclusions Our findings suggest that in early RA, the intermediate monocytes do not correlate with bone characteristics, despite positive correlation with circulating CXCR3(+) Th17 cells. Future longitudinal studies in patients with longer disease duration are required to fully explore the potential of intermediate monocytes to drive bone loss in RA.
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| 13. |
- Drevinge, Christina, 1983, et al.
(författare)
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Perilipin 5 is protective in the ischemic heart
- 2016
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 219, s. 446-454
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Tidskriftsartikel (refereegranskat)abstract
- Background: Myocardial ischemia is associated with alterations in cardiac metabolism, resulting in decreased fatty acid oxidation and increased lipid accumulation. Here we investigate how myocardial lipid content and dynamics affect the function of the ischemic heart, and focus on the role of the lipid droplet protein perilipin 5 (Plin5) in the pathophysiology of myocardial ischemia. Methods and results: We generated Plin5(-/-) mice and found that Plin5 deficiency dramatically reduced the triglyceride content in the heart. Under normal conditions, Plin5(-/-) mice maintained a close to normal heart function by decreasing fatty acid uptake and increasing glucose uptake, thus preserving the energy balance. However, during stress or myocardial ischemia, Plin5 deficiency resulted in myocardial reduced substrate availability, severely reduced heart function and increased mortality. Importantly, analysis of a human cohort with suspected coronary artery disease showed that a common noncoding polymorphism, rs884164, decreases the cardiac expression of PLIN5 and is associated with reduced heart function following myocardial ischemia, indicating a role for Plin5 in cardiac dysfunction. Conclusion: Our findings indicate that Plin5 deficiency alters cardiac lipid metabolism and associates with reduced survival following myocardial ischemia, suggesting that Plin5 plays a beneficial role in the heart following ischemia. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.
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| 14. |
- Humeniuk, Piotr, et al.
(författare)
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Profiling of innate and adaptive immune cells during influenza virus infection reveals sex bias in invariant natural killer T (iNKT) cells
- 2023
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Ingår i: Immunity, Inflammation and Disease. - 2050-4527. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Influenza A virus (IAV) infection leads to significant morbidity and mortality. Biological sex influences the immune responses to IAV infection, resulting in higher mortality in women of reproductive age. Previous studies revealed increased activation of T and B cells in female mice after IAV infection, but extensive analysis of sex differences in both innate and adaptive immune cells over time is lacking. Invariant natural killer T (iNKT) cells are fast-reacting forces and modulators of immune responses that are important to IAV immunity, but it is not known if the presence and function of iNKT cells differ between females and males. The aim of this study was to determine immunological mechanisms that contribute to the increased disease severity in female mice during IAV infection. Methods: Female and male mice were infected with mouse-adapted IAV and monitored for weight loss and survival. Immune cell populations and cytokine expression in bronchoalveolar lavage fluid, lung, and mediastinal lymph node were determined at three time points after infection using flow cytometry and ELISA. Results: The results reveal increased severity and mortality in adult female mice compared to age- matched males. Female mice show larger increases in innate and adaptive immune cell populations and cytokine production in lung compared to mock on Day 6 postinfection. On Day 9 postinfection, female mice express higher numbers of iNKT cells in lung and liver compared to males. Conclusions: This comprehensive analysis of immune cells and cytokines over time following IAV infection reveals increased leukocyte expansion and stronger proinflammatory cytokine responses in female mice during disease initiation. Furthermore, this is the first study to report a sex bias in iNKT cell populations after IAV infection. The data suggests that the process of recovery from IAV-induced airway inflammation is associated with increased expansion of several different iNKT cell subpopulations in female mice.
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| 15. |
- Lionikaite, Vikte, et al.
(författare)
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Vitamin A decreases the anabolic bone response to mechanical loading by suppressing bone formation
- 2019
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Ingår i: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - : Federation of American Societies for Experimental Biology. - 1530-6860 .- 0892-6638. ; 33:4, s. 5237-5247
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Tidskriftsartikel (refereegranskat)abstract
- Increased vitamin A consumption is associated with decreased cortical bone mass and increased fracture risk in humans. Rodent studies have demonstrated that hypervitaminosis A increases cortical bone resorption, whereas the importance of the effects on bone formation is less well defined. We used an experimental model of increased bone formation by loading of the tibiae to investigate the effect of vitamin A on bone formation. Control [retinol activity equivalents (RAE) 4.5 µg/g chow] or vitamin A (RAE 60 µg/g chow) diets were given to female C57BL/6N mice for 4 wk, after which the tibiae were subjected to axial loading on alternate days for 2 wk, while the diets were continued. Vitamin A inhibited the loading-induced increase in trabecular and cortical bone volume. This was attributed to inhibition of loading-induced increase in osteoblast number and activity, and expression of osteoblastic genes Sp7, Alpl, and Col1a1 in cortical bone. Vitamin A, loading, and combination thereof also resulted in site-specific effects on bone composition measured by Raman spectroscopy. In summary, a clinically relevant dose of vitamin A suppresses the loading-induced gain of bone mass by decreasing bone formation. These observations may have implications for regulation of bone mass caused by physical activity and the risk of osteoporosis in humans.-Lionikaite, V., Henning, P., Drevinge, C., Shah, F. A., Palmquist, A., Wikström, P., Windahl, S. H., Lerner, U. H. Vitamin A decreases the anabolic bone response to mechanical loading by suppressing bone formation.
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| 16. |
- Mardani, Ismena, et al.
(författare)
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Plin2-deficiency reduces lipophagy and results in increased lipid accumulation in the heart.
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Myocardial dysfunction is commonly associated with accumulation of cardiac lipid droplets (LDs). Perilipin 2 (Plin2) is a LD protein that is involved in LD formation, stability and trafficking events within the cell. Even though Plin2 is highly expressed in the heart, little is known about its role in myocardial lipid storage. A recent report shows that cardiac overexpression of Plin2 result in massive myocardial steatosis suggesting that Plin2 stabilizes LDs. In this study, we hypothesized that deficiency in Plin2 would result in reduced myocardial lipid storage. In contrast to our hypothesis, we found increased accumulation of triglycerides in hearts, and specifically in cardiomyocytes, from Plin2-/- mice. Although Plin2-/- mice had markedly enhanced lipid levels in the heart, they had normal heart function under baseline conditions and under mild stress. However, after an induced myocardial infarction, stroke volume and cardiac output were reduced in Plin2-/- mice compared with Plin2+/+ mice. We further demonstrated that the increased triglyceride accumulation in Plin2-deficient hearts was caused by altered lipophagy. Together, our data show that Plin2 is important for proper hydrolysis of LDs.
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