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Cardiovasc. Med."],"abstract":"<jats:p>Coronary microvascular dysfunction (CMD) represents a pivotal pathological hallmark across diverse cardiovascular pathologies, the progression of which is tightly coupled to systemic chronic inflammation. Clinically, CMD presents as ischemia with non-obstructive coronary arteries (INOCAs) and myocardial infarction with non-obstructive coronary arteries (MINOCAs), and contributes substantially to heart failure with preserved ejection fraction (HFpEF). Moving beyond conventional risk-factor stratification, this review dissects the mechanistic pathways through which individual comorbidities compromise coronary microcirculatory integrity. In hypertension, increased mechanical wall stress activates proinflammatory Nuclear factor \u03baB (NF-\u03baB)\u2013mitogen-activated protein kinases (MAPK) signaling cascades. In contrast, in diabetes, chronic hyperglycemia drives microvascular injury through the reactive oxygen species (ROS)\u2013advanced glycation end-products (AGEs) axis and Protein Kinase C (PKC)-dependent pathways. In obesity, adipokine dysregulation and gut-derived metabolites, notably trimethylamine N-oxide (TMAO), promote NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, a central mechanism in obesity-related CMD. In the setting of heart failure (HF) and cardiomyopathies, damage-associated molecular pattern (DAMP)\u2013Toll-like receptor (TLR) interactions and TGF-\u03b2\/Smad signaling promote capillary rarefaction and interstitial fibrosis, thereby linking systemic inflammation to structural microvascular remodeling. Furthermore, both autoimmune-mediated endotheliitis and virus-induced cytokine surges reduce nitric oxide (NO) bioavailability and impair coronary flow reserve (CFR). Thus, by integrating emerging therapeutic strategies, including interleukin-1\u03b2 (IL-1\u03b2) antagonists, SGLT2 inhibitors, and selected traditional medicines, we highlight approaches aimed at restoring microvascular homeostasis. Finally, we propose a personalized framework that leverages multi-omics profiling and artificial intelligence (AI) to modulate the inflammatory milieu, positioning inflammation-targeted interventions as a fundamental strategy for CMD prevention and management.<\/jats:p>","DOI":"10.31083\/rcm51873","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:57:11Z","timestamp":1790693831000},"source":"Crossref","is-referenced-by-count":0,"title":["Chronic Inflammation and Coronary Microvascular Dysfunction"],"prefix":"10.31083","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0340-062X","authenticated-orcid":true,"given":"Huijing","family":"Yao","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, 030032 Taiyuan, Shanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4562-9421","authenticated-orcid":true,"given":"Jiangwei","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, 030032 Taiyuan, Shanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8908-5217","authenticated-orcid":true,"given":"Luqun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, 030032 Taiyuan, Shanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6224-8480","authenticated-orcid":true,"given":"Ruiying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, 030032 Taiyuan, Shanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9416-3921","authenticated-orcid":true,"given":"Yuanyuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, 030032 Taiyuan, Shanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Crea F, Bairey Merz CN, Beltrame JF, Kaski JC, Ogawa H, Ong P, et al. 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